Case report: Novel frameshift mutation in LAMA2 gene causing congenital muscular dystrophy type 1A

The authors describe a patient who presented at two months of age with delayed psychomotor development, peripheral hypotonia, and muscle weakness. Whole-exome sequencing revealed two compound heterozygous variants in the LAMA2 gene: a previously reported nonsense variant (c.4198C>T) and a novel frameshift duplication (c.9227_9243dup). The patient's clinical course included elevated creatine kinase levels, abnormal brain MRI, myopathic changes on electromyogram, and complications such as severe scoliosis, hip dysplasia, and feeding difficulties requiring gastrostomy. The authors note the patient's phenotype aligns with the classic, severe early-onset form of CMD1A associated with biallelic loss-of-function variants. The study's primary limitation is the lack of functional analysis to confirm the pathogenic mechanism of the novel variant, as muscle biopsy could not be performed. The implications are that this report expands the genetic spectrum of CMD1A and highlights the utility of next-generation sequencing for diagnosis, especially in regions with limited prevalence data.