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 The Journal is open and publishes original unpublished articles, review topics, clinical case reports, relevant short communications, letters to the editor, as well as related opinions expressed in editorials.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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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.
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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.
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Advances and Perspectives of Genetic Pathologies in the 21st century.
Introduction: The discovery of deoxyribonucleic acid in 1953 marks the difference between classical genetics that was based on clinical observation to make diagnoses and perform genomic modifications empirically, which triggered a series of genetic aberrations that compromise the dignity of the human being and the new genetics, an era that allowed understanding the starting point in the mechanisms of regulation and gene expression and its role when coding DNA which has allowed the study of diseases of genetic or hereditary origin and give a targeted treatment. The new genetics brings with it novel tools to objectify the alterations that occur either at the level of genes, chromosomes or multifactorial disorders and to be able to identify and classify them in a pertinent manner, simplifying the understanding of these pathologies. Objective: This article aims to keep the scientific community updated on the different genetic pathologies and their classification taking into account the nomenclature and key points of each one. Methodology: A review of scientific articles was performed in databases such as Pubmed, Web of Science, Dynamed and Uptodate, with search terms for artificial intelligence in medicine, clinical research, legal framework, bioethical principles, automated analysis, among others. No language restrictions were applied. Medical subject headings (MeSH) were used. Additionally, reference lists, review articles and grey literature were manually searched for relevant articles not captured in the electronic scan. Conclusion: Human genetics and its pathologies are of constant interest, since through its knowledge different DNA variants of the coding and replication process are explained, knowing the latest definitions covering the subject is of great importance for its understanding.
Detection of a genetic variant of Apert syndrome
Introduction: Apert syndrome (AS), or acrocephalosyndactyly type I, is an autosomal dominant congenital disorder caused by a mutation in the FGFR2 gene, essential during embryonic development. It is characterized by craniosynostosis, midface hypoplasia and syndactyly. Although rare, its incidence is 1/100,000 to 1/160,000 live births, with a prevalence of 1 to 9 cases per 100,000 persons. Prenatal diagnosis is complex due to its similarity to other congenital syndromes. Objective: This article analyzes the genetic and molecular characterization of a patient diagnosed with Apert syndrome. Methodology: Informed consent was obtained and a clinical history and physical examination were performed. Blood samples were collected for paraclinical and molecular tests, as well as imaging studies. Results: The results showed phenotypic characteristics compatible with the syndrome, such as strabismus, proptosis and anterior plagiocephaly-type craniosynostosis. Genetic studies detected a pathogenic variant in the FGFR2 gene (c.755C>G) and a variant of uncertain significance (c.532C>T). Discussion: The FGFR2 mutation (c.755C>G) is one of the most frequent in AS and is suggested to affect receptor specificity, leading to suppression of osteoblast apoptosis, resulting in the phenotypic features of the syndrome. Conclusion: Although the variant of uncertain significance (c.532C>T) has deleterious features, no other cases with this variant have been reported. Currently, the patient has not presented additional deterioration and the prognosis remains uncertain. Further molecular studies are considered necessary to investigate this new variant and its clinical implications.
West Syndrome: spectrum of disorders with diagnostic and therapeutic challenges
Introduction: West syndrome (WS) is a rare epileptic encephalopathy of multifactorial etiology, characterized by epileptic spasms, psychomotor delay, and hypsarrhythmia on electroencephalogram. Its prevalence is 1.5 to 2 per 10,000 children under 10 years, with an incidence of 1 per 2,000-4,000 live births. Objective: This article describes the clinical characteristics of a pediatric patient with WS in a developing country context. Materials and methods: With informed consent, the clinical history was performed, detecting psychomotor delay at 6 months, manifested by loss of social smile and gross motor skills. Physical examination revealed generalized hypotonia, desaturation, and bradycardia. Neuroimaging ruled out organic abnormalities; however, the electroencephalogram (EEG) showed hypsarrhythmia, confirming the diagnosis of West syndrome by meeting the classic clinical triad. Results and discussion: Male patient of 6 months, firstborn, born by cesarean section at 39 weeks due to hypoxic encephalopathy, with negative STORCH and toxicological tests. He presented to the emergency room with four episodes of spastic movements in the upper limbs, which spontaneously resolved without loss of consciousness, during the previous month. Currently, at 12 years old, the patient is in remission, without seizure episodes for over 10 years. He shows adequate social and family adaptation, with academic performance appropriate for his age group. Cognitive tests indicate borderline performance, suggesting the presence of ADHD, with no evidence of underlying cognitive deficit.
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.
Chromoanagenesis and Erythroderma as diagnostic clues in a critically ill patient
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.
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De novo genetic variant in epileptic encephalopathy: Importance of specific diagnosis
Introduction: Early infantile epileptic encephalopathies (EIEE) are rare syndromes that affect neurological development. The etiology has been uncertain for a long time, but advances in genetics have identified numerous associated genes. Variants in the CYFIP2 gene have been linked to EIEE. Clinical case: An 11-year-old female born at term without complications, with microcephaly, synophrys, and short neck. No relevant family history. At one month, she developed generalized seizures and delayed neurodevelopment, progressing to severe spastic quadriparesis, requiring gastrostomy and tracheostomy, with paroxysmal discharges on electroencephalogram. She received multiple anticonvulsant medications and ketogenic therapy. Complete individual exome sequencing and analysis of deletions and duplications were requested. Individual complete exome + deletions and duplications analysis (CNV) identified a probably pathogenic heterozygous variant in the CYFIP2 gene variant c.259C>T (p.Arg87Cys) missense type, allelic ratio (VAF) 0.45. The results of this molecular study support the diagnosis of developmental and epileptic encephalopathy de novo. Discussion: Developmental and epileptic encephalopathy (EED) disorders are severe conditions that begin in childhood, characterized by epileptic seizures, abnormalities in the electroencephalogram, and deterioration of neurodevelopment. Genetic EEDs are associated with variants in various genes related to cellular and neuronal functions. The CYFIP2 gene, on chromosome 5q33.3, encodes protein 2 that interacts with FMRP (fragile X mental retardation protein), playing a crucial role in neurological development. De novo variants, such as nonsense mutations and truncation in CYFIP2, are associated with intellectual disability, seizures, and muscle hypotonia. Advancements in genomics are improving the understanding of epilepsy, impacting targeted treatment, prognosis, and patient counseling. Childhood epilepsy has a heterogeneous genetic basis, and some patients without previous diagnosis can now receive one, crucial for the implementation of precision medicine.
early infantil epileptic encephalophathy
Hypotonic syndrome as a manifestation of an ultra-rare disease caused by a new and de novo variant in the PLA2G6 gene
Introduction: congenital hypotonia, a rare condition that encompasses various neuromuscular disorders, can have a genetic origin, such as infantile neuroaxonal dystrophy (inad), an ultra-rare neurodegenerative disorder of unknown prevalence. Objective: to utilize genomic techniques for the precision diagnosis of low-prevalence neuromuscular diseases. Materials and methods: case report of an infant, without a family history of genetic diseases, normal pregnancy, hypotonia at birth, neurodevelopmental regression, nystagmus, strabismus, and cerebellar atrophy. Due to the suspicion of an autosomal recessive vs de novo inherited disease, genetic sequencing studies using ngs (next-generation sequencing) + cnv (copy number variations) were requested for genes related to congenital hypotonia (1,621 genes). Results: two heterozygous variants were identified (compound heterozygote for the pla2g6 gene), the first variant classified as probably pathogenic, a duplication of 5 nucleobases at position 1,914 of the cdna, in exon 14 of the gene. The second variant, classified as pathogenic, involves a change from guanine to adenine at position 2,081 of the cdna, in exon 15 of the gene. Variants in this gene are associated with three autosomal recessive medical conditions: infantile neuroaxonal dystrophy 1, neurodegeneration with brain iron accumulation 2b, and parkinsons disease 14. Discussion and conclusion: congenital hypotonia, linked to disorders such as inad, is difficult to diagnose conventionally. Deleterious variants in the pla2g6 gene, located on chromosome 22, are associated with three autosomal recessive hereditary conditions, including inad, with manifestations before 3 years of age, neurological symptoms, mortality within the first decade, and multiple complications. Genomic technologies, including reverse phenotyping, are fundamental in understanding its genetic basis, phenotypic heterogeneity, guiding targeted treatment, prognosis, follow-up, genetic counseling, and heritability risk, bringing us closer to anticipatory, preventive, and precision medicine, especially in ultra-rare conditions.
De novo variant in the COL1A1 gene associated with orphan genetic disease: Osteogenesis Imperfecta type I
Introduction: Osteogenesis Imperfecta (OI), is known as a disorder characterized by bone weakness and high risk of fractures, of genetic origin, known as brittle bone disease. It has a high burden of morbidity and mortality, associated with the presence of pain and functional limitation for those who present it. Fragility in the bones has been described by structural variants of the Collagen 1 genes (COL1A1 and COL1A2) among others, with an estimated prevalence between 1/15,000 and 1/20,000 cases in live newborns. The timely diagnosis of the disease allows to initiate targeted therapeutic alternatives, prevent complications, provide genetic counseling on risk of heritability, follow-up guidelines, prognosis approaching personalized medicine. Case Presentation: Female patient 8 years old, with clinical history of several fractures secondary to mild trauma (metatarsal left foot, right hand finger and ipsilateral foot), with other diagnoses of bilateral otosclerosis requiring hearing aids, precocious puberty, on physical examination with facial dysmorphias given by prominent broad forehead, mild blue tint sclerae, irregular teeth with dentin wear, ligament hyperlaxity, no cognitive-behavioral compromise and no other alterations.Within the paraclinical approach with hypercalcemia, hypercalciuria and hyperphosphatemia, other paraclinical evaluation of bone metabolism in normal reference range, within the imaging studies with total spine radiography with mild lumbar dextro convex dextro scoliosis, and anterolisthesis of L5 over S1, and radiographs showing areas of consolidation by fractures previously described, renal and urinary tract ultrasound with mild bilateral ectasia and 15% residue in bladder emptying. The patient was the product of non-consanguineous parents, with no known family history of genetic connective tissue diseases. Due to the clinical history and physical examination, a molecular sequencing + CNVs (Copy Number Variations) study was requested by NGS (Next-Generation Sequencing) for genes related to collagenopathies. Results: Molecular study sequencing + CNVs by NGS for genes related to collagenopathies in which a heterozygous pathogenic variant c.3652G>A; p.Ala1218Thr in the COL1A1 gene is detected, which supports the diagnosis of osteogenesis imperfecta type I of autosomal dominant inheritance. Conclusion: Osteogenesis imperfecta is a disease of genetic origin, rare, reported for many years, with phenotypic, endotypic and genotypic variability, so that undertake early identification strategies impact on the natural history of the disease contributing to the development of preventive medicine, personalized, predictive, accurate, participatory in order to be performed at the population level; through this case it is intended to raise awareness of the importance of early diagnosis and genotype-phenotype correlation that allows to establish targeted actions, to know specific pathophysiological mechanisms, to sub-classify collagenopathies, contributing to the increase of medical-scientific knowledge about the expression of the disease and the tendency to hyper-personalization.
Summary Year 2024, Volume 2, Issue 1 Published: April 30th, 2024 Editors and Reviewers The following team of professionals from different health areas participated in the preparation of this issue. Jorge D. Méndez-Ríos, MD, MS, PhD. Physician and Molecular Geneticist – Canada Dr. Lorena Salazar García, PhD. Molecular Geneticist – Spain Dra. Lina Johanna Moreno Giraldo, MD. Pediatric Geneticist – Colombia Dr. Indira Herrera Pediatric Geneticist - Republic of Panama Dr. Johan Serrano. Internal Medicine - Republic of Panama
Multimodal characterization of pediatric patients with neuromuscular diseases in southwestern Colombia.
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.
Strengthening partnerships for an academic goal
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
Current genomic diagnostic challenges in Hemophagocytic Syndromes in pediatrics: Case report
Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is a disease of the autoimmune system that presents with an excessive inflammatory syndrome caused by activated T lymphocytes and histiocytosis. It occurs with autosomal recessive inheritance linked to the chromosome X. Approximately 90% of diagnosed children are under 2 years of age and the incidence is approximately 0.12 per 100,000. It can be divided into five subtypes depending on the causative genetic variant. The most involved pathogenic variants are in the perforin 1 (PRF1) and UNC-13 protein homolog D (UNC13D) genes. Clinical case: The case of an 11-year-old preadolescent is presented, with a history of recurrent infections, who presents with convulsive syndrome associated with fever, low weight and height for age, hepatomegaly and cognitive disability. In the initial approach, infectious, immunological, hematological, metabolic and oncological diseases are ruled out. The clinical exome for primary immunodeficiencies shows a homozygous pathogenic variant p.A91V in the PRF1 gene of autosomal recessive inheritance, a result related to familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Discussion and conclusion: The altered PRF1 conformational change reduces the cytotoxic activity of the protein and causes disease. Patients carrying defects in the PRF1 gene are vulnerable to infections, autoimmune diseases and malignant tumors. With a defined and precise diagnosis, it is possible to guide health actions, follow-up guidelines, evaluation of heritability risk through an index case in order to find other possible carriers, carry out complete genetic counseling, implement and initiate targeted treatments that reduce the morbidity and mortality associated with this pathology. Currently, there are several studies in different phases of research on molecules that may intervene in the natural history of the disease.
Familial hemophagocytic lymphohistiocytosis
Genomic variants associated with inborn errors in carbohydrate metabolism in southwestern Colombia
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.
Aggrecanopathies: Report of a Spondyloepiphyseal Dysplasia Kimberley type (SEDK) in a family, caused by a previously undescribed likely pathogenic variant of the ACAN gene
The study of patients with short stature is complex and requires diagnostic algorithms in which the evaluation by Genetics is essential, seeking to rule out genetic syndromes that may explain the patient's manifestations. Among these possible causes, skeletal dysplasias should always be considered as a diagnostic possibility. We present the case of a family in which in the proband and in his progenitor a previously undescribed probably pathogenic variant was detected in the ACAN gene which encodes the Aggrecan Proteoglycan (PG), a fundamental component in the endochondral bone growth and in the articular cartilage, and whose alteration in heterozygous state produces Kimberley type Skeletal Spóndyloepiphyseal Dysplasia (SEDK) and other disorders known as aggrecanopathies. Molecular genetic analyses are becoming mandatory studies to achieve an accurate diagnosis in these cases. It is expected that the study of these conditions will shed light for a better understanding of the pathophysiology of osteoarthritis and for the development of new treatments for its management, given its high prevalence in older adults and the fact that aggrecan degeneration plays a central role in it.
Characterization of new genes involved in prostate cancer metastasis.
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.
Awareness of rare genetic diseases in daily clinical practice
In this issue, we are pleased to present 4 multidisciplinary papers that include disciplines such as Pediatric Genetics, Hematology, and Nephrology. These high quality papers represent the efforts of months of specialist colleagues in the area of multidisciplinary clinical genetics. Each contribution represents a tool for education and teaching at multiple levels of medical learning.
Characterization and prevalence of comorbidities in pediatric patients with Down syndrome in the Dominican Republic
This study analyzes the prevalence and characteristics of comorbidities in 534 children with Down Syndrome (DS) in the Dominican Republic, between 2018 and 2022. The research reveals early detection of DS, with an equal gender distribution. Most cases resulted from nondisjunction, with a significant association between advanced maternal age and increased risk of DS. About 62.2% of the children had comorbidities, with cardiac conditions being the most prevalent, followed by endocrine and neurologic comorbidities, mainly hypothyroidism and seizure disorders. Ophthalmic and otorhinolaryngologic conditions were also common, with strabismus and hypoacusis standing out. The findings emphasize the need for early and comprehensive management adapted to the individual and regional characteristics of patients with DS.
Case Report: Osteodysplastic Gerodermia in Panama
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.