Background: Merosin-deficient congenital muscular dystrophy (MDC1A) is a rare autosomal recessive genetic disease occurred due to mutations in the LAMA2 gene. This study investigated the molecular genetics of three Iranian MDC1A patients who manifested hypotonia, muscle weakness at birth, elevated levels of creatine kinase, and normal magnetic resonance imaging before the age of six months
Methods: Peripheral blood samples were collected from three unrelated patients and their families after obtaining informed written consents. Genomic DNA was extracted and sequenced using next-generation sequencing, followed by Sanger confirmation.
Results: Sequencing results revealed a known missense mutation, c.8665G>A, and two novel heterozygous sequencing variants affecting splicing, c.397-4_c.478del and c.7452-1G>A, in the LAMA2 gene. Reverse transcriptase-PCR analysis showed that a new intronic variant, c.7452-1G>A, produced aberrant splicing pattern in the patient.
Conclusion: This study expands the mutation spectrum of LAMA2 and assists in the diagnosis, genetic counseling, and prenatal diagnosis of the affected families.
Keywords: Creatine kinase; Genetic counseling; Mutation; Reverse transcriptase polymerase chain reaction.