A novel compound heterozygous variant in LAMA2 gene in a family with merosin-deficient congenital muscular dystrophy.

LAMA2 encodes the alpha-2 subunit of a protein called Laminin. It consists of three subunits Y; alpha, beta and gamma. Alpha2 subunit from LAMA2 gene along with beta-2 and gamma-2 forms laminin-2 protein. This protein is necessary for assembly of basement membrane in skeletal muscle cells, Schwann cells, astrocytes and pericytes. More than 100 LAMA2 variant identified so far which cause recessive form of muscular dystrophy (MD) either a severe form, congenital (CMD) or mild form, limb-girdle (LGMD). Patient with LAMA2 MD suffered from muscle weakness, elevated creatine kinase, facial dysmorphism, peripheral motor neuropathy, epilepsy/seizure, developmental delay, and white matter changes in brain MRI. In this study, we conducted whole exome sequencing (WES) to investigate molecular etiology of patients with CMD in one family with non-consanguineous marriage from Iran. WES has identified a novel compound heterozygous variant, [c.2049_2050del (p.Arg683Serfs*21)]; [c.2857-2 A > G (p.?)], in the proband. The identified variant was confirmed by Sanger sequencing and its segregation within the family was verified. Subsequently, in-silico analysis was performed to map the protein-protein interaction network between LAMA2 and proteins implicated in CMD pathogenesis. Our findings may be considered valuable molecular and clinical insights for improving our understanding of CMD, particularly regarding LAMA2 variants. Furthermore, this finding gives new insights to laboratorians, genetic counselors and clinicians for determining at-risk couples in the prenatal diagnosis (PND) program.