Genetics and Clinical Genomics

Editorial Board- Vol 2 Num 3 2024

Journal Genetics and Clinical Genomics — 2024-12-05

GENETICS AND CLINICAL GENOMICS JOURNAL

*Advancing Precision Medicine Through Research*

Volume 2, Issue 3

December 2024

Editorial Work for this issue provided by:

Dr. Jorge D. Méndez-Ríos

Dr. Horacio Lucero

Dr. Katlin Annyana De La Rosa Poueriet

Dr. Daniel E. Austin

INDEX

Editorial

A Genomic Revolution: Advancing Health and Knowledge in Latin America

Jorge David Méndez Ríos

Case report

Hypotonic syndrome as a manifestation of an ultra-rare disease caused by a new and de novo variant in the PLA2G6 gene

Jenny Adriana Morán Fernández, Lina Johanna Moreno Giraldo

De novo variant in the COL1A1 gene associated with orphan genetic disease: Osteogenesis Imperfecta type I

Jhonatan Alzate Valencia, Lina-Johanna Moreno-Giraldo

De novo genetic variant in epileptic encephalopathy: Importance of specific diagnosis

Johana Marcela Morán Fernández, Lina Johanna Moreno Giraldo

Detection of a genetic variant of Apert syndrome

Daniela Lynett, María Paola Lubo López, Laura Andrea Rojas Arbelaez, Paula Andrea Rodríguez Ocampo, Lev Bladimir Ramirez, Daniel Jimenez, Luis Gustavo Celis Regalado, Nathalia Fonque Ojeda, Gabriela García Montoya

Literature Review

Advances and Perspectives of Genetic Pathologies in the 21st century.

Paula Andrea Rodríguez Ocampo, David Luna Salazar, Karen Dayana Saavedra Pérez, Daniela Lynett Flórez, Luis Gustavo Celis Regalado

Editorial
Infomedic International
CMP #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)
eISSN 2953-3139 (Spanish)

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

Hypotonic syndrome as a manifestation of an ultra-rare disease caused by a new and de novo variant in the PLA2G6 gene

Jenny Adriana Morán Fernández — 2024-11-25

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

Jhonatan Alzate Valencia — 2024-11-25

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.

De novo genetic variant in epileptic encephalopathy: Importance of specific diagnosis

Johana Marcela Morán Fernández — 2024-11-25

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.

Detection of a genetic variant of Apert syndrome

Daniela Lynett — 2024-11-27

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.

Advances and Perspectives of Genetic Pathologies in the 21st century.

Paula Andrea Rodríguez Ocampo — 2024-11-28

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.

A Genomic Revolution: Advancing Health and Knowledge in Latin America

Jorge David Méndez Ríos — 2024-12-05

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.