Genetics and Clinical Genomics

Chromoanagenesis and Erythroderma as diagnostic clues in a critically ill patient

Enrique Daniel Austin-Ward — 2024-08-31

We report the case of a patient with severe multisystemic failure in which massive chromosomal changes in mosaic state were detected, which are considered to be associated with the possible underlying pathology: a T-cell lymphoproliferative syndrome. The patient also presented a case of Erythroderma of unknown cause several years earlier, with a progressive decline in her physical condition. The spectrum of clinical manifestations is then presented as a nonspecific paraneoplastic cutaneous picture of several years of evolution and findings of chromoanagenesis in the last phase of a lymphoproliferative morbid process. The new techniques of genetic analysis make it possible to obtain data to clarify the diagnostic processes and to identify a serious disorganization of the genetic information considered to be responsible for neoplastic changes.

Case Report: Osteodysplastic Gerodermia in Panama

Indira Herrera Rodriguez — 2024-08-31

ABSTRACT: Gerodermia osteodysplastica (GO) is a rare genetic disease in which the inheritance is autosomal recessive within Cutis laxa disorders, it is characterized by a lax and wrinkled skin, osteoporosis leading to spontaneous fractures, congenital dislocation of the hips, hyperextensible joints, progeroid features, developmental delay and intellectual deficit. This is a condition caused by genetic mutations in the GORAB gene (1q24.2). We present the case of a 3-month-old infant with the typical phenotype of this condition, lax and wrinkled skin, specially the hands and feet, in addition to a knee dislocation. A panel testing for connective tissue disorders was performed, which identified an alteration in the GORAB gene, confirming the diagnosis de Gerodermia osteodysplastica.

Multimodal characterization of pediatric patients with neuromuscular diseases in southwestern Colombia.

Tatiana Marcela Jiménez Martínez — 2024-08-31

Introduction: Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) are rare but severe genetic neuromuscular diseases in the pediatric population with high burden of morbidity and mortality. Despite advances in their understanding and search for targeted therapeutic options, there are still gaps in timely detection, characterization, patient follow-up, active search for carriers and in some Latin American countries no neonatal screening. Objective: To characterize clinically, paraclinically, imaging and molecularly patients with presumptive and confirmed diagnosis of Duchenne muscular dystrophy (DMD) and Spinal Muscular Atrophy (SMA) attended in a pediatric center of reference and excellence in Southwestern Colombia. Materials and Methods: Observational cross-sectional study in patients under 18 years of age with ICD-10 diagnoses related to DMD and SMA. Data were exported to an Excel matrix in Office 365 version 2403, and then to IBM SPSS version 29 to perform a univariate analysis, measures of central tendency and dispersion were used for numerical variables, considering their distribution, and absolute frequencies and percentages for qualitative variables. Results: After reviewing 954 medical records belonging to a pediatric care center in Southwestern Colombia between 2015 - 2021, 422 cases related to Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) were identified; excluding duplicates and unrelated records, from these, 99 cases were randomly selected for a comprehensive analysis using OpenEpi version 3.01, distributed in two groups: SMA (n=23) and DMD (n=76). Patients confirmed with Duchenne Muscular Dystrophy (DMD) showed symptom onset at 54.5 ± 29.0 months and diagnosis at 98.8 ± 34.9 months, being more common in males with hypotonia and elevated creatin kinase (CK) levels, 54.5% had cognitive impairment and 88. 2% had family history, in Spinal Muscular Atrophy (SMA), the onset of symptoms was at 28.9 ± 37.7 months and diagnosis at 37.9 ± 38.2 months, being predominant in females with areflexia and fasciculations, there were no records of cognitive function in confirmed patients, and 21.7% had family history of SMA, in addition to slight elevations of CK. In the SMA group, 9 cases were molecularly confirmed and 3 were supported by medical records; in contrast, in the DMD group, 22 cases had molecular confirmation, but 9 had annotations in medical records, although these reports were incomplete. Conclusions: Early suspicion and diagnosis of these progressive neurodegenerative diseases characterized by high morbidity and mortality rates is critical to impact the holistic approach patients should receive. Given the continuous advance in diagnostic methods and innovative and targeted therapeutic options (hyperpersonalization medicine), it is necessary to create complete medical-clinical registries and "big data", which have all the current tools available (multimodal diagnostic options) to facilitate patient re-contact, follow-up and to be able to offer personalized, precision care that improves the quality of life of patients and their families, contributing to the generation of integrated and targeted public policies.

Genomic variants associated with inborn errors in carbohydrate metabolism in southwestern Colombia

Jaime David Viafara Belalcazar — 2024-08-31

Introduction: Carbohydrate Inborn Errors of Metabolism (IEMs) result from disruption of the catabolic or anabolic pathways of different carbohydrates, fructose, galactose and glycogen being the most common and belong to a heterogeneous group of disorders that may be inherited or may occur as a result of spontaneous genetic variants. In IEM, there are altered carbohydrate pathways, both catabolic and anabolic pathways, including fructose, galactose and glycogen metabolism, resulting in a heterogeneous group of disorders. However, data on these pathologies in Colombia are scarce. The aim of our study was to identify genomic variants associated with carbohydrate IEM in the southwestern Colombian population lacking clinical diagnosis. Results: We performed a cross-sectional study, sequencing 320 exomes and classifying variants according to standard guidelines. We identified 286 variants, including 206 new variants and 73 benign or probably benign variants. Notably, six variants in genes such as GALT, GAK1, ALDOB, GAA and SLC2A1 were of uncertain significance, and one pathogenic variant in the GALT gene was associated with classic galactosemia. Interestingly, 18% were intronic, 5% missense, 10% synonymous, and 67% unreported variants.

Conclusions: These findings highlight the need for early diagnostic programs to implement targeted treatments, including transdisciplinary management to minimize morbidity and mortality. Genetic counseling and risk education are crucial, facilitating anticipatory and preventive medicine approaches, thus advancing precision medicine.

Characterization of new genes involved in prostate cancer metastasis.

Bary Bigay Mercedes — 2024-08-31

Introduction: Our work addresses a literature review conducted between January 2019 and September 2023, the importance of BRCA1, BRCA2, AR and PTEN genes in the pathogenesis, prognosis and treatment of prostate cancer, especially in its metastatic castration-resistant form (mCRPC), is highlighted. BRCA1 and BRCA2 genes are identified as key markers for predicting cancer aggressiveness, suggesting the need for targeted therapies and strict surveillance. The adaptability of cancer cells and variability in androgen receptor (AR) expression limit the effectiveness of therapies focused solely on AR, pointing to the importance of identifying alternative pathways and biomarkers for more effective treatment. PTEN function is directly related to disease progression, and its alteration suggests potential therapeutic approaches. However, the heterogeneity of cancer cells and complexity of molecular pathways present significant challenges to the development of universal therapies. Conclusion: The findings promote future research to confirm the applicability of these genes as biomarkers and to develop personalized treatment strategies in prostate cancer.

Strengthening partnerships for an academic goal

Jorge D. Mendez-Rios — 2024-08-31

In this edition, we present two original articles that address genetic variants of relevance associated with carbohydrate metabolism diseases and neuromuscular disorders in a specific region of Colombia. These findings underline the urgent need to train healthcare professionals for the early diagnosis of these pathologies and to involve the state in promoting and generating knowledge about neglected diseases.

We also include a report on an extraordinarily rare hemato-oncological case, documenting the massive accumulation of copy number variants. This report strikingly illustrates the clinical importance of copy variant studies in hemato-oncology, highlighting the first recorded case of Geroderma osteodysplastica in Panama.

Finally, we present a comprehensive literature review that explores the genes associated with prostate cancer, covering research published between 2019 and 2023. This review highlights the critical influence of the genes BRCA1, BRCA2, AR, and PTEN in the pathogenesis of prostate cancer, especially in its castration-resistant metastatic form (mCRPC). The identification of BRCA1 and BRCA2 as markers of aggressiveness, along with the relevance of PTEN in disease progression, reinforces the need to develop more specific therapies and explore additional biomarkers, given the complex landscape presented by cancer cells. These articles reflect the unwavering commitment of our researchers to generating knowledge from our Latin American region, significantly contributing to global science. We hope that this edition will be of great help and encouragement to your scientific work.

We want to take this opportunity to thank the editors, reviewers, and readers for their valuable contributions to the realization of this publication. The role of the editor is essential in the construction and maintenance of the scientific quality of our journal. Their vision and dedication ensure that each published article not only meets the highest academic standards but also reflects relevance and impact in the scientific community. Without their leadership and guidance, this rigorous process would not be possible. This type of partnership can only endure with a clear and honest vision of the long-term impact of education.
Reviewers, with their expert knowledge and meticulous analysis, represent the backbone of the peer review process. Their commitment to thoroughly examining each manuscript and providing constructive criticism is essential to ensuring the accuracy, reliability, and novelty of the research we share with our audience. Often working behind the scenes, reviewers significantly contribute to science, enhancing the quality of works and guiding authors towards excellence.

Finally, our readers play an essential role in the cycle of scientific communication. Their interest, curiosity, and practical application of the knowledge acquired bring the published research to life. Each article becomes a bridge between research and practice when it is read, discussed, and applied by you, our readers. Your feedback and active participation motivate us to continue improving and to remain a reliable source of scientific information. Together, editors, reviewers, and readers form an essential triangle that supports and strengthens the mission of our journal: to advance scientific knowledge and contribute to the improvement of health and well-being in society. To all of you, our deepest gratitude.

Sincerely,

Jorge D. Méndez-Ríos
Editor-in-Chief
Genetics and Clinical Genomics

Editorial Team - Vol 2 Num 2 2024

Journal Genetics and Clinical Genomics — 2024-08-31

Editorial work

The following team of professionals from different health areas participated in the preparation of this issue.

Dr. Jorge D. Méndez-Ríos, MD, MS, PhD.
Hospital Université Laval, Québec, Canadá

Dr. Luis Gustavo Celis, MSc.
Universidad de La Sabana, Chía, Colombia

Dr. Carolina Rivera Nieto, MD, MSc
Bogotá, Colombia

Dr. Ricardo Fernández-Ramires, PhD
Genetic Counselor. Grupo Chileno de Cáncer Hereditario (GCCH)

Rosamaria Mora, Arch, MSc.
Cordination

Editorial
Infomedic International
Consultorios Médicos Paitilla #430
Panama, Rep. of Panama
Published for the Collaborative Network for Genetics and Clinical Genomics.
First edition: June 2023.
Current edition: August 2024.
eISSN L 3072-9610 (English)

This publication is distributed under the CC-BY-SA license.