Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Whole Exome Sequencing Identified a Novel Lama2 Frameshift Variant Causing Merosin-Deficient Congenital Muscular Dystrophy in a Patient With Cardiomyopathy, and Autism-Like Behavior Publisher Pubmed



Nouri Z1, 2 ; Sarmadi A2 ; Narrei S1 ; Sehhati M3 ; Tabatabaiefar MA2, 4, 5
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Research and Development, ERYTHROGEN Medical Genetics Lab, Isfahan, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Bioinformatics, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. GenTArget Corp (GTaC), Deputy of Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Neuromuscular Disorders Published:2022


Abstract

Muscular dystrophy (MD) is a group of multiple muscle diseases, which causes severely impaired motor ability, degeneration and dysfunctions in the musculoskeletal system, respiratory failure and feeding difficulties. LAMA2-related MD is caused by pathogenic variants in the LAMA2 gene, encoding laminin a2 chain, a component of the skeletal muscle extracellular matrix protein laminin-α2β1γ1. We performed clinical examination and molecular genetic analysis in a patient with congenital MD (CMD), and autism-like phenotype. We performed whole exome sequencing (WES) to find possible genetic etiology of CMD in an Iranian non-consanguineous patient. The pathogenicity of the variants was assessed using various Bioinformatics tools. American College of Medical Genetics and Genomics (ACMG) guidelines were used to interpret the variant and Sanger sequencing in the patient and her family was applied for the confirmation of the variant. WES results showed a novel frameshift homozygous variant (p.Tyr1313LeufsTer4) in the LAMA2 gene leading to the CMD phenotype. This variant resides in a highly conserved region and was found to be co-segregating in the family. It fulfils the criteria of being pathogenic. We successfully identified a novel LAMA2 pathogenic variant in an Iranian patient suffering from CMD and autism using WES. Identification of disease-causing variant in autosomal recessive disorders such as CMD can be useful in genetic counseling, prenatal diagnosis, and predicting prognosis of the disease. © 2022
Related Docs
View other Related Docs
1. Causative Variants Linked With Limb Girdle Muscular Dystrophy in an Iranian Population: 6 Novel Variants, Molecular Genetics and Genomic Medicine (2023)
2. Next-Generation Sequencing Reveals a Novel Pathological Mutation in the Tmc1 Gene Causing Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Kindred, International Journal of Pediatric Otorhinolaryngology (2019)
3. Homozygosity Mapping and Direct Sequencing Identify a Novel Pathogenic Variant in the Cisd2 Gene in an Iranian Wolfram Syndrome Family, Acta Diabetologica (2020)
4. A Novel Homozygote Pathogenic Variant in the Diaph1 Gene Associated With Seizures, Cortical Blindness, and Microcephaly Syndrome (Scbms): Report of a Family and Literature Review, Molecular Genetics and Genomic Medicine (2024)
5. Molecular and Phenotypical Findings of a Novel De Novo Syngap1 Gene Variant in an 11-Year-Old Iranian Boy With Intellectual Disability, Lab Medicine (2024)
6. The First Report of Iranian Registry of Patients With Spinal Muscular Atrophy, Journal of Neuromuscular Diseases (2023)
7. Whole Exome Sequencing Revealed a Novel Gjb1 Pathogenic Variant and a Rare Bscl2 Mutation in Two Iranian Large Pedigrees With Multiple Affected Cases of Charcot-Marie-Tooth, International Journal of Molecular and Cellular Medicine (2019)
8. Using Whole Exome Sequencing in Determining the Genetic Cause of Parkinson Disease in an Iranian Family, Neurology Asia (2021)
Experts (# of related papers)
View all Related Experts
Mohammad Amin Tabatabaiefar (11)
Keivan Basiri (4)
Other Related Docs
9. Two Novel Mutations in Aldh18a1 and Spg11 Genes Found by Wholeexome Sequencing in Spastic Paraplegia Disease Patients in Iran, Genomics and Informatics (2022)
10. A Homozygous Nonsense Variant in Uvssa Causes Uv‑Sensitive Syndrome From Very Large Kindred: The First Report From Iran, Advanced Biomedical Research (2023)
11. On Genotype-Phenotype Relationship of Dystrophinopathies Among Iranian Population, Current Journal of Neurology (2023)
12. Ultra-Rare Variants Identify Biological Pathways and Candidate Genes in the Pathobiology of Non-Syndromic Cleft Palate Only, Biomolecules (2023)
13. A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred, Journal of Dermatological Science (2017)
14. Use of in Silico Tools for Classification of Novel Missense Mutations Identified in Dystrophin Gene in Developing Countries, Gene (2014)
15. A Novel Heterozygous Truncating Variant in the Ago1 Gene in an Iranian Family With Schizophrenia As an Unreported Symptom, Annals of Human Genetics (2023)
16. A Recurrent Homozygous Missense Dpm3 Variant Leads to Muscle and Brain Disease, Clinical Genetics (2022)
17. Clinical Features in a Large Iranian Family With a Limb-Girdle Congenital Myasthenic Syndrome Due to a Mutation in Dpagt1, Neuromuscular Disorders (2013)
18. A Novel De Novo Frameshift Variant in the Chd2 Gene Related to Intellectual and Developmental Disability, Seizures and Speech Problems, Molecular Genetics and Genomic Medicine (2024)
19. Mfsd8 Gene Mutations; Evidence for Phenotypic Heterogeneity, Ophthalmic Genetics (2019)
20. A Novel Mettl5 Variant Disrupting a Donor Splice Site Leads to Primary Microcephaly-Related Intellectual Disability in an Iranian Family: Clinical Features and Literature Review, Journal of Genetics (2023)
21. Infantile Neuroaxonal Dystrophy in Two Cases: Siblings With Different Presentations, Iranian Journal of Child Neurology (2022)
22. Detection of Intragenic Smn1 Mutations in Spinal Muscular Atrophy Patients With a Single Copy of Smn1, Journal of Child Neurology (2015)
23. Whole Exome Sequencing Revealed Variants in Four Genes Underlying X-Linked Intellectual Disability in Four Iranian Families: Novel Deleterious Variants and Clinical Features With the Review of Literature, BMC Medical Genomics (2023)
24. Identification of Novel Mutations in Tpk1 and Slc19a3 Genes in Families Exhibiting Thiamine Metabolism Dysfunction Syndrome, Heliyon (2024)
25. Novel Kiaa0753 Mutations Extend the Phenotype of Skeletal Ciliopathies, Scientific Reports (2017)
26. Phenotype and Genotype Heterogeneity of Pla2g6-Associated Neurodegeneration in a Cohort of Pediatric and Adult Patients, Orphanet Journal of Rare Diseases (2023)
27. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)