Abstract
Abstract
Background
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a rare autosomal recessive genetic condition caused by deleterious mutations in the LAMA2 gene encoding the laminin-α2 chain. It is the most frequent subtype of congenital muscular dystrophies (CMDs) characterized by total laminin-α2 deficiency with muscle weakness at birth or in the first six months of life. To the best of our knowledge, this study reports the first molecular diagnosis and genetic defect of this heterogeneous form of CMD performed in a Moroccan medical genetic center using next-generation sequencing (NGS). It allows us to expand the mutational spectrum of the LAMA2 gene.
Case presentation
We report the case of a female Moroccan child with clinical and paraclinical features in favor of a CMD. She has global congenital hypotonia with generalized muscle weakness, psychomotor retardation, increased serum creatine kinase, and normal brain scan at the age of six months. Targeted NGS leads to the identification of a novel homozygous nonsense mutation c.2217G > A, p.(Trp739*) in the exon 16 of LAMA2. Sanger sequencing confirmed this mutation in the affected patient and showed that her parents are heterozygous carriers.
Conclusions
A modern genetic analysis by NGS improves the genetic diagnosis pathway for adequate genetic counseling of affected families more precisely. An accession number from the National Center for Biotechnology Information (NCBI) ClinVar database was retrieved for this novel LAMA2 mutation.
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics
Reference18 articles.
1. Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, Tome FM, Schwartz K, Fardeau M, Tryggvason K, et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet. 1995;11(2):216–8.
2. Durbeej M. Laminin-alpha2 chain-deficient congenital muscular dystrophy: pathophysiology and development of treatment. Curr Top Membr. 2015;76:31–60.
3. Beytia Mde L, Dekomien G, Hoffjan S, Haug V, Anastasopoulos C, Kirschner J. High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency. Mol Cell Probes. 2014;28(4):118–22.
4. Tran KT, Le VS, Vu CD, Nguyen LT. A novel de novo variant of LAMA2 contributes to merosin deficient congenital muscular dystrophy type 1A: case report. Biomed Rep. 2020;12(2):46–50.
5. Mah JK, Korngut L, Fiest KM, Dykeman J, Day LJ, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of the muscular dystrophies. Can J Neurol Sci. 2016;43(1):163–77.
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