Novel mutation (c.8725T>C) in two siblings with late-onset LAMA2-related muscular dystrophy

Abstract

Objective: LAMA2 mutation-related muscular dystrophy is classified into two clinical phenotypes: severe early-onset congenital muscular dystrophy and mild late- onset muscular dystrophy. According to several reported cases, late-onset LAMA2-related muscular dystrophy clinically shows the limb girdle muscular dystrophy pattern and has been considered to be associated with the partial expression of laminin α2. Methods: We describe here a patient initially suspected of having limb girdle muscular dystrophy, but was later diagnosed with late-onset LAMA2-related muscular dystrophy. Results: We found compound heterozygous variations on the patient's LAMA2 gene, a heterozygous nonsense variation in exon 49 (c.6955C>T/p.Arg2319*), previously reported as a pathogenic variation, and a heterozygous missense variation in exon 62 (c.8725T>C/p.Cys2909Arg), which is a novel variation. Her and her sister's brain magnetic resonance images (MRI) revealed diffuse symmetric high signal unmyelinated changes in bilateral cerebral white matter. Muscle tissue sections were stained with hematoxylin and eosin, and showed mild muscle fiber size variation, a few necrotic and regenerative muscle fibers, and endomysial edema Immunohistochemical staining for laminin α2 showed a reduction compared with the control. Conclusion: We suggest that this novel missense mutation is the likely pathogenic mechanism through the genotype–phenotype correlation and the annotation process.