The Journal Genetics and Clinical Genomics is a multi-country, peer-reviewed journal with publications in both Spanish and English. Its publications will be quarterly with its first issue in early 2023. It is affiliated to the Latin American Network for Cooperation in Genomics and Clinical Genetics, of the Editorial Infomedic International. The focus of the journal is to share experiences and knowledge in this field in Spanish-speaking countries with contributions from experts from other continents. The projection of the journal is to become a reference center for the implementation of molecular diagnostics and personalized medicine. The Journal is open and publishes original unpublished articles, review topics, clinical case reports, relevant short communications, letters to the editor, as well as related opinions expressed in editorials. Manuscripts will be accepted for publication only if they have not been previously published. The journal has started with two publication options, free and open access. The free option allows any author to submit their manuscript at no additional cost. The open access version uses the CCBY 4.0 license, which allows placement of your manuscript in HTML version and free redistribution of the manuscript. The Journal assumes no responsibility for the consequences of the use of the information contained in its publications. They reflect the exclusive point of view of their authors. Editorial Address: Consultorio Médicos Paitilla, #430, Panama Rep. Panama, P.O. Box 12639. Email: ventas@infomedicint.com Editorial Office Email: editor@geneticalatam.com
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Chromosomal Triple Mosaicism in a Male with Turner Syndrome, 8p21.1–pter Deletion, and Yq Deletion: A First Case Report
We present the case of a male patient who was under medical observation as an infant due to cardiac malformations, microcephaly, dysmorphic features, and psychomotor developmental delay. Karyotyping revealed mosaicism for Turner syndrome and a deletion of the short arm of chromosome 8 (8p-). Fourteen years later, the patient developed refractory epilepsy, and the case was re-evaluated with molecular analysis to delineate the 8p deletion. This analysis broadened the scope of the loss and also detected an additional cell line exhibiting mosaicism with a partial loss of the long arm of the Y chromosome (Yq-), resulting in a mosaicism for three chromosomal abnormalities. However, the molecular technique was limited in its ability to identify that one of the cell lines contained X monosomy and the 8p- deletion. A new karyotype was subsequently performed, confirming the findings of the initial analysis. The patient's phenotype is described, and genotype-phenotype correlations are established, along with the influence and possible origins of structural and numerical chromosomal alterations on the patient's clinical presentation. This first case with these alterations in the same patient demonstrates the importance of complementary analytical techniques and the ideal future goal of routinely implementing simultaneous genetic analyses with complementary tests to improve our understanding of the genome and its potential alterations.
Copyright (c) 2026 This journal uses a CC-BY-NC-ND license for all material published. https://creativecommons.org/licenses/by-nc-nd/4.0
Cutaneous Leishmaniasis Mimicking Low-Grade Myofibroblastic Sarcoma: A Case Report from Resistencia, Chaco, Argentina
Background: Cutaneous leishmaniasis (CL) is an emerging vector-borne disease endemic in northern Argentina and may present with atypical clinical and histopathological features that mimic soft tissue neoplasms, leading to diagnostic delay and misclassification. Case presentation: A 19-year-old man from Resistencia, Chaco, Argentina, presented in January 2026 with a painful right inguinal mass and a progressive ulcerated lesion on the right flank. Initial histopathology showed a spindle cell proliferation interpreted as low-grade myofibroblastic sarcoma. Microbiological studies were negative. Definitive diagnosis was established by real-time polymerase chain reaction (PCR) with High-resolution melting analysis confirming the presence of Leishmania (Viannia) braziliensis. The patient received intramuscular meglumine antimoniate and showed marked clinical improvement. Conclusions: This case highlights the diagnostic challenge of CL when histopathology suggests a myofibroblastic sarcoma. In endemic areas, CL should be considered in the differential diagnosis of soft tissue masses, and molecular testing is essential when conventional studies are inconclusive.
Clinical Management and Therapeutic Advances in Pediatric Patients with Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
Introduction: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder frequently complicated by plexiform neurofibromas (PN), which cause severe functional impairment and present a complex therapeutic challenge. Methods: This descriptive case series evaluates four pediatric patients diagnosed with NF1 and progressive, symptomatic PN managed at a tertiary care children's hospital in Panama. Clinical records, histopathology, molecular treatment data, and serial Magnetic Resonance Imaging (MRI) or Computed Tomography scans were retrospectively analyzed to assess progression and treatment responses. Results: The cohort presented diverse manifestations, including orbital/craniofacial and spinal tumor involvement. Traditional surgical resections yielded limited efficacy due to the infiltrative nature of the lesions. However, targeted molecular therapy with the MEK inhibitor selumetinib initiated after traditional treatment failure led to substantial outcomes: Case 1 achieved a 27.7% volumetric tumor reduction within six months, and Case 3 demonstrated complete resolution of a paravertebral lesion concurrently with severe pain reduction (from 7 to 3 on the pain scale) and significant improvements in motor gait and quality of life. Conclusions: While surgical boundaries remain highly restricted in deep-tissue infiltrative PN, the introduction of targeted MEK inhibitors marks a pivotal therapeutic paradigm shift. Improving timely access to these therapies, alongside adequate monitoring, may help prevent further functional deterioration in selected pediatric patients, although larger, prospective studies are needed to confirm the magnitude and durability of this benefit.
Computational Structural Modeling of the TTN p.(Arg3936Ter) Variant in a Panamanian Patient with Dilated Cardiomyopathy
Background: Truncating variants in TTN are among the most frequent genetic causes of dilated cardiomyopathy. However, TTN encodes multiple tissue-specific isoforms through extensive alternative splicing, and the clinical significance of a given truncating variant can depend critically on which transcript is affected. Objectives: This study pursued three related aims for the TTN NM_133379.5:c.11806C>T; p.(Arg3936Ter) variant, previously identified in a Panamanian patient with dilated cardiomyopathy: (1) to consolidate its clinical interpretation using established genomic evidence and ACMG/AMP criteria; (2) to characterize the domain-level and structural consequence of the predicted truncation, combining protein domain annotation with AlphaFold2-based structural modeling of both the wild-type and truncated protein; and (3) to determine the transcript specificity of this consequence across annotated TTN isoforms and its predicted nonsense-mediated decay (NMD) status. Methods: We integrated variant annotation, population frequency, conservation scores, ACMG/AMP interpretation, InterProScan/Pfam domain annotation, Ensembl VEP consequence annotation across all annotated TTN transcripts, and AlphaFold2/ColabFold structural modeling (with a genuine multiple sequence alignment) of both wild-type and truncated protein fragments (residues 3399–4100 and 3399–3935, respectively, of isoform Novex-3, NP_596870.2). Structural similarity between models was assessed by rigid-body superposition (Kabsch algorithm) and independently cross-validated using the RCSB PDB pairwise structure alignment tool (TM-align). Results: The p.Arg3936Ter variant introduces a premature termination codon predicted to generate a truncated titin protein of 3,935 amino acids. Established genetic evidence — extreme rarity in population databases and strong evolutionary conservation — supported classification as Likely Pathogenic under ACMG/AMP criteria (PVS1, PM2). VEP annotation across 14 curated TTN transcripts showed that this genomic position is intronic in 91% of annotated transcripts and produces a stop-gained consequence exclusively in NM_133379.5 (Novex-3), the transcript used for clinical variant nomenclature. Within this transcript, the variant falls in exon 46 of 46 — the final exon — and is predicted to escape nonsense-mediated decay. InterProScan identified two immunoglobulin-like (I-set) domains in the encoded fragment; the truncation removes the second domain in its entirety. AlphaFold2 modeling of both the wild-type and truncated fragments (each with a real multiple sequence alignment) showed nearly identical mean confidence (pLDDT 56.5 vs. 55.2) and, on structural superposition, the retained domain aligned with an RMSD of 0.19 Å between wild-type and truncated models, confirming that the shared portion of the protein folds identically and that the only structural difference is the complete absence of the second domain. Conclusion: Established genomic and population-level evidence support a Likely Pathogenic, loss-of-function classification for the TTN p.Arg3936Ter variant. This structural consequence is specific to the Novex-3 isoform (NM_133379.5), escapes nonsense-mediated decay, and is expected to yield a stable truncated protein missing a complete immunoglobulin-like domain — a conclusion independently supported by domain annotation, AlphaFold2 modeling of both wild-type and truncated proteins, and quantitative structural alignment.
From Variants to Vision: Reframing Precision Medicine in Diverse Populations
This editorial emphasizes that true precision medicine can only be achieved when genomics is interpreted within the context of specific populations, healthcare systems, and clinical realities. Drawing on studies of thrombosis, rare syndromes, and cancer, it highlights that many genetic markers are not universally applicable, that genomic diagnostic capabilities are advancing faster than the clinical systems needed to act on them, and that significant inequalities in access to key technologies persist. Overall, it underscores the need to move from data-driven genomics toward a more contextualized, equitable, and clinically actionable approach to medicine.
Prevalence of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Variants in Patients and Controls in Panama
Background: Thrombosis is one of the leading causes of morbidity and mortality worldwide. Several genetic factors have been associated with increased thrombotic risk, including variants in Factor V Leiden (G1691A), prothrombin G20210A, and the C677T variant in the methylenetetrahydrofolate reductase gene (MTHFR). Identification of these variants may contribute to thrombotic risk assessment and clinical decision-making in patients with thromboembolic events or recurrent pregnancy loss. Methods: A case-control study was conducted to determine the prevalence of Factor V Leiden (G1691A), prothrombin G20210A, and methylenetetrahydrofolate reductase gene MTHFR C677T variants in a Panamanian population. A total of 105 patients with thrombosis and 105 controls were analyzed, in addition to 55 women with recurrent pregnancy loss and 55 controls without recurrent pregnancy loss or thrombosis. Results: Heterozygosity for Factor V Leiden was observed in 6.7% of patients with thrombosis and 1.0% of controls (OR 7.43;95% CI: 0.89–61.48). The prothrombin G20210A variant showed a moderate association with thrombosis (OR 2.58;95% CI: 0.48–13.58). These variants were not detected in women with recurrent pregnancy loss, and MTHFR C677T showed no association with thrombosis or recurrent pregnancy loss. Conclusion: Factor V Leiden and prothrombin G20210A variants were associated with an increased risk of thrombosis, whereas MTHFR C677T showed no association with thrombosis or recurrent pregnancy loss in the studied population.
Severe neonatal Costello syndrome caused by a de novo HRAS p.Gly12Cys variant: the role of whole-exome sequencing in differential diagnosis
Background: Costello syndrome is an ultra-rare RASopathy caused by gain-of-function mutations in the HRAS proto-oncogene, leading to constitutive activation of the RAS/MAPK signaling pathway and characterized by distinctive craniofacial features, multisystem involvement, and increased cancer risk. Case Presentation: We report a 37-week gestation male neonate with a prenatal diagnosis of severe polyhydramnios who presented at birth with coarse facies, macrocephaly, redundant skin, and severe multi-organ involvement initial chromosomal microarray analysis was normal (arr(X,Y)x1,(1–22)x2), but whole-exome sequencing identified a pathogenic heterozygous missense variant in the HRAS gene (c.34G >T p.Gly12Cys). Results: The clinical course was severe and progressive, with biventricular hypertrophic cardiomyopathy, complex arrhythmias, and prolonged dependence on mechanical ventilation, culminating in death at five months of age. Conclusions: This case highlights the diagnostic challenges associated with rare genetic disorders and underscores the importance of genomic sequencing as a fundamental diagnostic tool, while emphasizing genotype–phenotype correlations and the need for strict oncological surveillance due to the increased risk of malignancies such as rhabdomyosarcoma.
From Diagnostic Complexity to Precision Medicine: Integrating Cytogenetics, Molecular Biology, and Targeted Therapies
The continuing evolution of molecular medicine is transforming not only how diseases are diagnosed, but also how their mechanisms are understood and how patients are treated. Increasingly, complex clinical presentations require an integrated approach in which traditional clinical evaluation, pathology, cytogenetics, molecular diagnostics, computational biology, and targeted therapeutics complement one another. The articles presented in this issue illustrate this transition across a remarkably diverse spectrum of genetic, neoplastic, cardiovascular, and infectious diseases. The first article, Chromosomal Triple Mosaicism in a Male with Turner Syndrome, 8p21.1–pter Deletion, and Yq Deletion: A First Case Report, demonstrates the complexity that can underlie chromosomal disorders and the importance of combining complementary diagnostic methodologies. The identification of three chromosomally abnormal cell lines, including numerical and structural alterations involving the X, Y, and chromosome 8, highlights both the power and the limitations of individual genetic techniques. Importantly, this case reminds us that newer molecular approaches do not necessarily replace conventional cytogenetics. Rather, their greatest diagnostic value may emerge when they are interpreted together, particularly in patients with complex phenotypes that cannot be adequately explained by a single genomic finding. The second contribution, Clinical Management and Therapeutic Advances in Pediatric Patients with Neurofibromatosis Type 1 Associated Plexiform Neurofibromas, moves from molecular diagnosis to molecularly guided treatment. Plexiform neurofibromas remain among the most challenging manifestations of neurofibromatosis type 1, particularly when their infiltrative growth limits the effectiveness of surgical intervention. The experience presented in this pediatric case series illustrates the changing therapeutic landscape created by MEK inhibition. The clinical and radiological responses observed with selumetinib exemplify how understanding disease-associated signaling pathways can be translated into targeted interventions with the potential to improve function, reduce symptoms, and alter the clinical course of previously difficult-to-treat lesions. The third article, In Silico Structural Characterization of the Novel TTN p.Arg3936Ter Variant in Dilated Cardiomyopathy, explores another dimension of contemporary precision medicine: the interpretation of genetic variation at the transcript, protein-domain, and structural levels. The study emphasizes an increasingly important principle in genomic medicine—that the biological consequence of a variant cannot always be understood from its genomic position alone. Through integration of transcript annotation, ACMG/AMP interpretation, protein-domain analysis, nonsense-mediated decay prediction, and AlphaFold2-based structural modeling, the authors demonstrate an isoform-specific consequence of a truncating TTN variant. Such approaches illustrate the growing contribution of bioinformatics and structural prediction to the interpretation of clinically relevant genomic findings. Finally, Cutaneous Leishmaniasis Mimicking Low-Grade Myofibroblastic Sarcoma: A Case Report from Resistencia, Chaco, Argentina reminds us that precision diagnostics are equally important beyond inherited disease. The clinical and histopathological resemblance between cutaneous leishmaniasis and a soft tissue neoplasm created a significant diagnostic challenge, ultimately resolved through molecular detection of Leishmania (Viannia) braziliensis. This case underscores the importance of maintaining a broad differential diagnosis and integrating epidemiological context with pathology and molecular testing, particularly in regions where infectious diseases may present with unusual or misleading morphological features. Although these four contributions address very different diseases, they converge on a common message. Diagnostic accuracy increasingly depends on the ability to integrate information generated at multiple levels—from clinical phenotype and histopathology to chromosomes, DNA sequences, transcripts, protein structures, and molecular pathways. At the same time, the expanding availability of targeted therapies demonstrates that increasingly precise diagnosis has consequences that extend well beyond classification: it can directly influence clinical management. This issue therefore reflects a broader transformation taking place across medicine. Conventional diagnostic methods remain indispensable, but they are increasingly strengthened by molecular assays, genomic analysis, computational modeling, and mechanism-based therapeutics. The challenge ahead is not simply to adopt increasingly sophisticated technologies, but to determine how they can best complement established clinical and laboratory practices and how their benefits can be made accessible to the patients and populations who need them. Taken together, the studies presented in this issue demonstrate the value of interdisciplinary investigation and reinforce a fundamental principle of modern medicine: complex clinical problems are often best resolved not by a single technique, but by the thoughtful integration of complementary evidence.
High-grade serous ovarian cancer: from a Genetic perspective.
Introduction: In Mexico, ovarian cancer (OC) is the third leading cause of death from malingnant tumors in women aged 30 to 59. High-grade serous epithelial cell OC is the most frequent (70-80%). Its location, slow growth, and nonspecific syntoms often lead to detection at advanced clinical stages. The objetive of this study is ti descibe, from a genetic and molecular perspective, the characteristics of a sample of patients with high-grade serous ovarian carcinoma (HSOC). Methods: Women uderwent molecular studies of the BRCA1/2 genes using next-generetion sequencing and/or large rearrangement analysis. Results: Thirteen Mexican women were included, in whom variants in the BRCA1 gene were found in 61.5% of cases. Of these, 15.4% presented with deletion of exons 9-12, and 23% prsented variants that produce a reading frame shift involving the alteration of a non-conserved nucliotide, considered VPs; which fall within the "ovarian cancer cluster region" (OCCR) in exon 11 of BRCA1. Case 7 presents a VP and has no history of ovarian cancer (OC), and is a young patient. Case 8, with a VUS, shows a family history of OC and other related cancers across several generations. Conclusions: Molecular studies are of great importance in patients with SAG-OC.
Craniofacial Microsomia in Cat-Eye Syndrome: Rethinking the formation mechanism through cytogenetic clues
The wide spectrum of clinical and morphological manifestations turns the diagnosis of Craniofacial microsomia tricky, even more so having the overlap of phenotype with other comorbidities such as Cat-eye Syndrome. The distinction is established by cytogenetic tests, which may be a barrier in an underdevelopment/emergent country as Brazil. Here we report a patient with Craniofacial microsomia clinical manifestation that turned out to be a rare kind of Cat-eye Syndrome, the type II asymmetric. We also went 20 years back, through a literature review, pointing to gene contributions and rethinking the probable formation mechanisms of this complex chromosomal alteration of chromosome 22.
Deletion of chromosome 22q11.2 and its origin
Deletion of chromosome 22q11.2 is a common disorder and a constant subject of inquiry due to its variable expressivity. Independently of severity, ranging from severe (DiGeorge syndrome) to milder manifestations, carriers may have children with more severe phenotypes. Here, we present a mini-review focused on answering some questions, raising others, and exploring different points of view regarding the inheritance and formation mechanisms of the 22q11.2 deletion.
Vitamin D-dependent rickets type 1A due to pathogenic variant in CYP27B1:Case report
Clinical case: This is a case report of a one-year-old male infant with a history of chronic malnutrition and global developmental delay who was admitted to the Dr. José Renán Esquivel Children's Hospital with community-acquired pneumonia complicated by septic shock. Clinical and radiological findings: During his hospitalization, severe mineral metabolism disorders, multiple pathological fractures, and radiological findings consistent with severe rickets were documented. Biochemical findings: Biochemical studies revealed persistent hypocalcemia, marked elevation of alkaline phosphatase, and secondary hyperparathyroidism. Molecular diagnosis: Molecular study by whole exome sequencing identified a homozygous pathogenic variant in the CYP27B1 gene (NM_000785.4:c.602_611del; p.Val201AlafsTer31), confirming the diagnosis of vitamin D-dependent rickets type 1A. Treatment and outcome: Treatment with alfacalcidol and calcium supplementation was initiated, with a favorable initial clinical and biochemical response. Conclusion: This case highlights the importance of timely recognition of genetic forms of rickets and the use of effective therapeutic alternatives in settings where calcitriol is not available.
Genetics and Entropy: Turning our gaze toward the thermodynamics of biological systems
A particular physical magnitude governs our existence in an unsuspected way: entropy, formulated from the Second Law of Thermodynamics. This review seeks to move beyond its traditional conception as an abstract notion of physics and to present it as a fundamental key to understanding how we arise, organize, and ultimately fade away. Entropy is examined from a biological and genetic perspective, drawing on rigorous scientific literature, both contemporary and classical, for its conceptual foundation. We explore how biological systems do not challenge the laws of physics but rather exploit them to sustain life, maintaining internal order at the expense of exporting entropy to the environment. The contributions of Schrödinger, Prigogine, and Lehninger are revisited to describe organisms as self-replicating dissipative structures capable of persisting through the extraction of negative entropy from their surroundings. In addition, the work of contemporary physicists such as Carroll and Greene is used to examine the intricate relationship between evolution and entropy. The informational dimension of entropy is also addressed through DNA, understood not only as a molecule but as a biological language. Finally, cancer and aging are explored as divergent pathways of a shared entropic principle. From the perspective of genetics and biology, life can be understood as a precise choreography of energy and information, whose progressive dissipation threatens the very continuity of existence.
Copyright (c) 2025 This journal uses a CC-BY-NC-ND license for all material published. https://creativecommons.org/licenses/by-nc-nd/4.0
Letter to the Editor - Operational impact of entropy concepts in genetics and medical practice
The general trend in medical practice is to integrate new knowledge and perspectives on human beings that help enrich our understanding of the mechanisms that enable their existence and help us combat diseases or other conditions that affect them. This refinement of understanding and this integrative vision come from the convergence of various areas of knowledge, such as biology and physics, since reality is a whole, which, due to the limitations of human capabilities and in order to study it better, we have had to divide into parts in order to assimilate all the information it contains. In this sense, the concepts of entropy and its role as a modeling force of the vital phenomenon are fundamental to substantially improve this vision. They provide us with an interesting perspective on evolutionary processes and could provide us with very useful tools for the specialized management of patients.
Editorial - Case reports as regional references
Dear colleagues and readers, We are pleased to present this new issue of the journal, which brings together original contributions that reflect both the scientific depth and the growing regional leadership of biomedical research in Latin America. The articles included in this edition span conceptual reflection, molecular genetics, and clinically grounded case reports, offering readers a diverse and meaningful perspective on contemporary challenges in medicine and genomics. A distinctive feature of this issue is its engagement with fundamental questions about life and disease. The review article “Genetics and Entropy: Turning our gaze toward the thermodynamics of biological systems” proposes an integrative view that connects genetics, biology, and physics through the concept of entropy. By revisiting classical and modern scientific thought, the authors invite readers to consider biological organization, evolution, aging, and cancer as expressions of underlying thermodynamic principles. This discussion is further enriched by a Letter to the Editor from Panama, which reflects on entropy as a conceptual tool in medical practice and highlights its potential to deepen our understanding of human health and disease. The issue also places strong emphasis on rare genetic disorders through carefully documented case reports that illustrate real diagnostic and therapeutic challenges. From Panama, the report on vitamin D–dependent rickets type 1A caused by a pathogenic CYP27B1 variant underscores the importance of early genetic diagnosis and demonstrates how effective treatment strategies can be implemented even in settings where access to standard therapies is limited. Two contributions from Colombia address the clinical complexity of chromosomal duplication syndromes. The case describing 22q11.2 duplication syndrome highlights the wide phenotypic variability associated with this condition and reinforces the value of chromosomal microarray analysis in achieving accurate diagnosis and guiding management. In a similar vein, the report on 15q11–q13 duplication syndrome (Dup15q) illustrates how advanced genomic testing can clarify long-standing neurodevelopmental phenotypes, inform prognosis, and support appropriate genetic counseling for patients and families. Completing this issue is a review from Mexican authors examining miransertib as an emerging therapeutic option for Proteus syndrome, a rare disorder driven by abnormal activation of the PI3K/AKT pathway. This article provides a concise and clinically relevant overview of targeted therapy in a condition for which treatment options remain limited, emphasizing the growing role of precision medicine in rare diseases. Collectively, the articles in this issue highlight the strength of regional clinical experience, the increasing integration of genomic technologies into medical practice, and the importance of interdisciplinary thinking. They reflect a shared commitment to advancing knowledge while addressing the practical realities faced by clinicians and researchers in our region. We extend our sincere thanks to the authors and reviewers for their valuable contributions and invite our readers to engage with the insights and cases presented in this new issue. Sincerely, Dr. Jorge D. Méndez-Rios, Editor-in-Chief Genetics and Clinical Genomics
Miransertib and the PI3K/AKT pathway: an emerging therapeutic approach for Proteus syndrome
Introduction: Proteus syndrome is a rare disorder characterized by progressive tissue overgrowth associated with abnormal activation of the PI3K/AKT pathway, secondary to mutations in AKT1. Current therapeutic options are limited; however, miransertib, a selective AKT inhibitor, has emerged as a potential alternative by blocking the abnormally elevated activity of AKT1, a key mechanism underlying the dysregulated cellular proliferation that characterizes this disease. Objective: To describe the clinical, radiological, and functional outcomes of patients with Proteus syndrome treated with miransertib, and to evaluate its impact on lesion growth, mobility, and associated symptoms. Clinical cases: Four patients with Proteus syndrome are presented, including children, adolescents, and young adults, with variable clinical manifestations such as cerebriform connective tissue nevi, osseous overgrowth, musculoskeletal pain, functional limitation, and, in one case, associated neoplastic disease. Patients were treated with individualized miransertib dosing regimens and underwent clinical, functional, and imaging follow-up. Results: Treatment with miransertib was associated with a deceleration of lesion growth and, in some cases, a reduction in lesion size. Improvements in joint mobility, pain reduction, and stabilization of pulmonary and skeletal complications were also observed. In one patient, a partial tumor response was documented, with resolution of ascites, peritoneal implants, and portal vein thrombosis, achieving complete clinical remission after prolonged follow-up. Adverse effects were generally mild and manageable. Conclusion: Selective inhibition of the PI3K/AKT pathway with miransertib appears to slow lesion progression and improve function and quality of life in patients with Proteus syndrome, supporting the therapeutic potential of AKT inhibitors. Nevertheless, long-term studies with larger patient cohorts, evaluation of combination therapies, and identification of predictive biomarkers are required to confirm sustained efficacy and safety and to advance toward personalized medicine.
When Chromosome 15 Duplicates: A Clinical-Genetic Challenge
Background: Chromosome 15q11–q13 duplication syndrome (Dup15q) is a rare neurodevelopmental disorder caused by additional copies of a genomic region enriched in imprinted genes essential for normal neuronal function. It is commonly associated with autism spectrum disorder (ASD), epilepsy, hypotonia, global developmental delay, and intellectual disability. Case presentation: We report the case of a 31-year-old male with a longstanding history of refractory epilepsy, autism spectrum disorder, and intellectual disability. Genetic evaluation using array-comparative genomic hybridization (array-CGH) combined with single-nucleotide polymorphism (SNP) analysis identified a de novo interstitial heterozygous duplication of 10.03 Mb involving the 15q11.2–q13.3 region. The duplicated segment encompasses multiple genes with key roles in neurodevelopment, including UBE3A, GABRB3, GABRA5, SNRPN, and NDN. Parental testing by multiplex ligation-dependent probe amplification (MLPA) was negative, confirming a non-inherited origin. Establishing the molecular diagnosis allowed precise clinical classification, informed therapeutic decision-making, and enabled appropriate genetic counseling. Conclusion: This case illustrates the diagnostic value of array-CGH in patients with complex neurodevelopmental phenotypes and emphasizes the importance of early genetic assessment in individuals presenting with ASD and epilepsy. Identification of pathogenic copy number variants such as Dup15q has significant implications for prognosis, clinical management, and family counseling.
Phenotypic heterogeneity of Duplication Syndrome 22q11.2: relevance of genomic DNA analysis
Background: 22q11.2 duplication syndrome (22q11.2DupS) is a rare autosomal dominant disorder characterized by a broad spectrum of clinical manifestations, including intellectual disability, dysmorphic features, and congenital anomalies. The phenotypic heterogeneity of 22q11.2DupS complicates both clinical diagnosis and management. Traditional screening methods, such as fetal ultrasound, often fail to detect these abnormalities early, leading to delayed diagnoses however, advances in chromosomal microarray analysis (CMA) offer a promising opportunity to improve detection, particularly in high-risk pregnancies. Case presentation: This report describes a female patient with dysmorphic features, neurodevelopmental delay, and behavioral alterations, with no related family history or consanguinity. Genetic findings: The patient was diagnosed with 22q11.2DupS through genomic DNA analysis using the Agilent® SurePrint G3 Human CGH+SNP array, which identified a heterozygous interstitial duplication at chromosomal coordinates 22q11.22 affecting the TOP3B gene, currently not associated with any known pathology but implicated in genomic stability and cellular aging. Discussion: 22q11.2DupS is a rare chromosomal disorder with a wide phenotypic spectrum, including intellectual disability, dysmorphic features, and congenital anomalies despite increasing recognition, comprehensive descriptions of its full clinical spectrum remain limited, and similar duplications have been classified with varying degrees of pathogenicity in public databases. Conclusion: 22q11.2DupS represents a complex clinical challenge due to its broad phenotypic spectrum, and early detection through advanced genetic testing such as CGH+SNP microarray analysis, along with genetic counseling and therapies including cognitive-behavioral and speech therapy, is essential for effective management as no specific therapies are available, treatment remains symptomatic.
Prevalence of Metabolic Syndrome X in patients diagnosed with Chronic Kidney Disease undergoing dialysis
Introduction: Metabolic syndrome X (MSX) encompasses risk factors such as abdominal obesity, hypertension, dyslipidemia, and insulin resistance, which significantly increase cardiovascular morbidity and mortality. In patients with chronic kidney disease (CKD), the presence of MSX is even more relevant, as it accelerates disease progression and increases cardiovascular complications. A retrospective, descriptive study was conducted in which patients treated at the Hemodialysis Unit of Dr. Amador Guerrero Hospital were evaluated, and the presence of cardiovascular risk factors and components of MSX was quantified. Justification: Metabolic syndrome is highly prevalent in patients with chronic kidney disease and increases cardiovascular risk, making its identification essential to improve clinical outcomes. Methodology: Patients with chronic kidney disease undergoing dialysis in the province of Colón during 2005 were studied. Anthropometric and laboratory data were collected, and metabolic syndrome was diagnosed according to the NCEP/ATP III (2005) criteria. Data analysis was performed using EPI-INFO 6.0. Results: A prevalence of 23.7% of MSX was observed among patients treated at the unit. Of these patients, 88.9% presented abdominal obesity and arterial hypertension. However, only abdominal obesity and insulin resistance (measured as fasting hyperglycemia) were statistically significant for the presence of MSX in CKD patients, with reported ORs of 38.4 (95% CI: 3.88–379.70, p<0.05) and 6.28 (95% CI: 1.23–31.95, p<0.05), respectively. Conclusion: The prevalence of MSX in the studied population was 23.7%. Abdominal obesity and insulin resistance significantly increased the likelihood of MSX. Furthermore, current evidence suggests that genetic variants may predispose CKD patients to the development of MSX, opening new avenues for research.
Towards clinical genomics in Mexico: History and proposals
Clinical genomics is an essential tool for the diagnosis and management of genetic disorders; however, its development in Mexico has been limited and uneven. Despite recent progress, such as the establishment of new medical genetics residency programs and specialized clinical units, services remain highly centralized and diagnostic infrastructure is scarce. Most hospitals lack in-house genetic laboratories, forcing reliance on private or foreign services that are often prohibitively expensive, creating significant barriers for patients. Furthermore, there is a shortage of clinical geneticists and available positions in the public health system, contributing to a considerable lag in care. Initiatives such as the National Rare Disease Registry and the efforts of patient advocacy organizations (e.g., FEMEXER, AMAER, ANER) have increased visibility and support for individuals with genetic and rare diseases, but they cannot fully address the wide spectrum of conditions, particularly ultra-rare disorders. To overcome these challenges, five key priorities are proposed: strengthening public genomic diagnostic infrastructure, decentralizing clinical services, expanding training programs and job opportunities for clinical geneticists, consolidating a standardized national rare disease registry, and reinforcing collaboration between institutions and civil society. These actions are fundamental to ensuring the constitutional right to health and advancing equitable access to genomic medicine in Mexico.
Progress and Perspectives of Genetic Diagnosis in Panama
Genetic diagnosis in the field of medical genetics, which dates back to the pioneering efforts of Dr. John R. Ward, has experienced remarkable progress in Panama in recent years due to increased capacity, the growing number of specialized Panamanian professionals, and the development of all aspects related to this field within institutions such as the Social Security Fund, the Children's Hospital, the Gorgas Institute, and the INDICASAT Institute, among others. There has also been an increase in private offerings and industry support. The prospects for growth go hand in hand with the growing need for medical evaluation by geneticists, genetic diagnosis as part of the daily medical management of all specialties, and the short-term advent of personalized or precision medicine.
Advances in genetic diagnosis in Colombia
In Colombia, genetic diagnosis has advanced significantly over the past two decades, establishing itself as a key tool for prevention, early detection, and personalized medicine. The legal framework, including the Statutory Health Law, Resolution 5267 of 2017, and Law 1392, has ensured equitable access to genetic testing through the Health Benefits Plan. The country has incorporated massive sequencing technologies, genetic telemedicine, and clinical applications in oncology, pediatrics, and infectious diseases. However, challenges remain regarding infrastructure distribution, specialist training, administrative barriers, and specific regulation of genomic data. The consolidation of a national genomic medicine system and the integration of population databases stand out as strategic priorities to strengthen research and public health.
Editorial - Regional cooperation and integration for the advancement of genetics and clinical genomics
Clinical genetics in Latin America has experienced significant growth driven by the incorporation of molecular and cytogenetic technologies, as well as new therapeutic alternatives. This process has been accompanied by professional training and collaborative efforts aimed at consolidating precision diagnostic services. In this issue of the Genetics and Clinical Genomics Journal, contributions from experts across several countries highlight advances and challenges in the region. Among them are the implementation of legislative frameworks, the strengthening of local diagnostic capacities, and the need to expand public health services. The issue also includes original studies addressing the relationship between metabolic syndrome and chronic kidney disease in hemodialysis patients, along with an analysis of gene structure and regulatory elements with direct implications for clinical practice. Taken together, these contributions reflect the achievements and current challenges of clinical genetics in Latin America and its role in advancing precision medicine.
The Landscape of Clinical Genetics in Honduras, Central America
In Honduras, clinical genetics is still at an early stage of development despite the country’s rich genetic diversity and important research contributions from isolated academic groups. Distinct populations, such as Indigenous communities and the Afro-descendant Garifuna, illustrate unique genetic profiles and founder effects with direct public health relevance. However, the practice of clinical genetics in Honduras faces major barriers, including the absence of nationally trained specialists, limited diagnostic capacity, lack of neonatal screening legislation, and the absence of registries for genetic diseases. Recent initiatives, including civil society advocacy and the planned COCINH LAB-Honduras project, signal opportunities to advance diagnostics, research, and training. To fully realize this potential, Honduras must invest in human resources, establish legal and ethical frameworks, and foster regional and international collaborations. Strengthening clinical genetics is essential for Honduras to address its population’s health needs and to ensure equitable access to modern genomic medicine.
Structure of a gene and its control elements
Knowledge of the structure, regulation, and function of genes is a fundamental pillar of molecular biology and modern medicine. Genes are DNA sequences that contain the information necessary to produce functional proteins or RNA, and are not only made up of coding regions (exons), but also introns and regulatory elements such as promoters, enhancers, and silencers. Mutations in any of these regions can alter normal cellular function and lead to various diseases. The regulation of gene expression ensures that not all genes are activated at the same time, but rather in a controlled manner depending on the cell type, stage of development, or environmental conditions. This control is mediated by transcription factors, epigenetic modifications such as DNA methylation, and the action of non-coding RNAs, mechanisms that allow multiple specialized cell types to be generated from the same DNA sequence. The function of genes is reflected in the products they encode, whether proteins or RNA, which participate in vital processes such as metabolism, cell signaling, or DNA repair. Genetic variants can cause loss of function, as in the case of cystic fibrosis due to mutations in the CFTR gene, or gain of function, as occurs in certain oncogenes involved in cancer.
Understanding Molecular and Genomic Pathophysiology: Key to Effective Molecular Diagnosis
In this issue, we present three original studies that address various rare genetic conditions. The first focuses on West syndrome and provides a detailed analysis of its diagnosis along with a proposed therapeutic approach to this complex condition. The study emphasizes the importance of early diagnosis and timely, appropriate intervention. Researchers from the Universidad de La Sabana in Chía, Colombia, have done an outstanding job highlighting key aspects of clinical management and listing the genes associated with this disorder. The second original study was conducted by the team at the Genomics Institute of the Social Security Fund in Panama. The report includes 78 cases and describes the variants found in the SERPINA1 gene, which is associated with alpha-1 antitrypsin deficiency due to proteolytic degradation. This work is of great importance as it represents one of the first studies of its kind in Panama and the region. The third original contribution, conducted by medical students, presents an analysis of the evidence listed in OMIM regarding the MTHFR gene, which has been linked to multiple conditions such as neural tube defects, schizophrenia, thrombosis, and abnormalities in homocysteine levels. This review highlights the most compelling evidence while also identifying gaps in our understanding of this gene and its clinical impact. The study was carried out by an enthusiastic group of students from the School of Medicine at the Interamerican University of Panama. Finally, a research group from the Chromomed Center in the Dominican Republic presents a case study and review of a rare instance of diploid/triploid mosaicism. An exhaustive investigation was conducted using multiple molecular, cytogenetic, and imaging methods. This study stands out for the complexity of the case and the richness of the descriptive evidence, making a significant contribution to the understanding of clinical genetics and genomics in our region. Undoubtedly, these contributions are pioneering and offer significant academic value for training and advancing our understanding of molecular diagnostic technologies. Although such technologies have supported genetic diagnosis in Latin America for decades, ongoing training and the development of a new generation of professionals focused on the molecular mechanisms of disease are still needed. Medicine today is personalized and will continue to focus on the molecular details of each condition, ultimately leading to better healthcare for our population.
Evaluation and classification of articles related to the MTHFR gene and OMIM evidence.
Introduction: The MTHFR gene, located at 1p36.22, is involved in the conversion of homocysteine to methionine via folate metabolism, which is essential for DNA, RNA, and protein synthesis. Variants such as C677T and A1298C have been associated with neural tube defects, thrombosis, schizophrenia, and homocystinuria due to MTHFR deficiency—an autosomal recessive condition characterized by toxic accumulation of homocysteine. Methodology: A systematic search was conducted using the OMIM database. Tasks were distributed among team members to ensure validated content, collaborative writing, and consistent structure. Results: A total of 113 studies were identified: 11 case-control studies, 9 genetic association studies, 8 meta-analyses, 4 letters to the editor, 4 negative association studies, and only 2 cohort and 2 genomic studies. Mutations affect the activity of the MTHFR enzyme, leading to multisystem dysfunctions. Homocystinuria presents neurological, ocular, skeletal, and vascular manifestations. No conclusive evidence of haploinsufficiency or triplosensitivity was found according to ClinGen. Discussion: The literature shows sustained interest in MTHFR, although results are mixed. Functional variants may contribute to complex disorders, but epigenetic, environmental, and gene-gene interactions also play a role. The limited number of longitudinal and molecular studies restricts a comprehensive understanding of the gene. Conclusion: MTHFR is a key genetic marker in personalized medicine. The predominance of observational studies highlights the need to diversify methodological approaches and functionally validate its clinical role, encouraging genetic screening and preventive interventions with folate.
First Reported Case Of Diploid/Triploid Mosaicism In The Dominican Republic
This study details the case of a one-year-old girl displaying significant overgrowth and bodily asymmetry, including right-side hemihypertrophy and delayed psychomotor development. A molar pregnancy was suspected during prenatal care, with postnatal evaluations revealing skeletal and cutaneous anomalies. Extensive genetic analysis uncovered a rare case of diploid/triploid mosaicism, evidenced by the coexistence of cells with both normal (46,XX) and abnormal (69,XXX) chromosomal compositions. This discovery is pivotal in elucidating the etiology of the clinical symptoms and emphasizes the critical role of thorough genetic counseling and comprehensive clinical management in the treatment of complex genetic disorders.
A Genomic Revolution: Advancing Health and Knowledge in Latin America
Editorial: Pioneering Genetics and Genomics Research for Regional Progress As we enter the second year of the Genetics and Clinical Genomics Journal, there is much anticipation for the future of this field in the region. It’s remarkable to see how far we’ve come in such a short time. This journal was born from a vision to bring together the best of genetics and genomics research and make a meaningful impact on healthcare and education in our region. That vision is becoming a reality, thanks to the incredible contributions of our authors and the support of our readers. This issue features an impressive selection of articles that highlight the power of genomic research to transform lives. Our Case Reports section includes stories of rare and complex conditions where genetics has played a critical role: In Hypotonic syndrome as a manifestation of an ultra-rare disease caused by a novel de novo variant in the PLA2G6 gene, we see the intricate process of solving a diagnostic mystery and its profound implications for patient care. De novo variant in the COL1A1 gene associated with an orphan genetic disease: Type I osteogenesis imperfecta sheds light on a rare condition that challenges both families and clinicians but also presents opportunities for targeted treatments. De novo genetic variant in Epileptic Encephalopathy: The importance of specific diagnosis highlights how pinpointing a genetic cause can lead to more effective therapeutic strategies. Finally, Detection of a genetic variant in Apert syndrome examines a condition that, while rare, has significant developmental and therapeutic implications. Our Review Articles, Literature review and Advances and perspectives on genetic pathologies in the 21st century, provide valuable overviews of current trends and emerging possibilities, serving as essential guides for anyone engaged in genetic research or clinical practice. Why This Matters Genetics and genomics are no longer rare disciplines they’re reshaping how we understand health and disease. In our region, this knowledge has the potential to address long-standing healthcare inequities, ensuring that advances in precision medicine benefit all communities, not just a select few. Equally exciting is the role genetics can play in education. Training the next generation of healthcare providers and researchers to harness the power of genomics is essential. By investing in education, we’re laying the groundwork for a future where genomic medicine is fully integrated into everyday practice. This journal is a testament to what’s possible when we work together—scientists, clinicians, educators, and policymakers. It’s an invitation to keep pushing boundaries, asking tough questions, and finding answers that matter. Thank you for joining us on this journey. I hope you find this issue inspiring, thought-provoking, and a reminder of the incredible potential within genetics and genomics to create a healthier, more equitable world.
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Protease S and Z inhibitor genotypes in the SERPINA1 gene in patients with COPD in the Republic of Panama
Background: Alpha-1-Antitrypsin (AAT) is a protein that inhibits protease, especially Trypsin. AAT deficiency can cause lung diseases such as early emphysema, mainly affecting the Anglo-Saxon population; this was considered to be a rare condition in Panama. This study aimed to determine the prevalence of Alpha-1-Antitrypsin Deficiency (AATD) and allele frequency, in patients with COPD. Methods: Cross-sectional intervention study, in patients with COPD diagnosis in Panama. All patients’ AAT levels were determined with blood samples, by nephelometry. Those with AAT levels <116 mg/dL were subjected to genotyping with the real-time PCR test (AAT-mpx RealFast), which detects the protease inhibitor (PI) *M, *S y *Z of the SERPINA1 gene simultaneously. Results: 78 patients were included, 55 (70.5%) had AAT levels <116 mg/dL. The genotype distribution for these was as follows: PI*MM in 15 (27.3%), PI*MZ in 37 (67.3%), PI*MS in 2 (3.6%), and PI*SS in 1 (1,8%). Conclusion: Our findings demonstrate that AATD frequency is low in COPD patients. However, we have a high frequency of the heterozygous PI*MZ allele, which could be a future risk factor. Methods: Cross-sectional intervention study, in patients with COPD diagnosis in Panama. All patients’ AAT levels were determined with blood samples, by nephelometry. Those with AAT levels <116 mg/dL were subjected to genotyping with the real-time PCR test (AAT-mpx RealFast), which detects the protease inhibitor (PI) *M, *S y *Z of the SERPINA1 gene simultaneously. Results: 78 patients were included, 55 (70.5%) had AAT levels <116 mg/dL. The genotype distribution for these was as follows: PI*MM in 15 (27.3%), PI*MZ in 37 (67.3%), PI*MS in 2 (3.6%), and PI*SS in 1 (1,8%). Conclusion: Our findings demonstrate that AATD frequency is low in COPD patients. However, we have a high frequency of the heterozygous PI*MZ allele, which could be a future risk factor.
Copyright (c) 2024 This journal uses a CC-BY-NC license for all material published. https://www.infomedicintl.com/index.php/politicas-editoriales/