R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B

Background Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM),conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene toidentify the relationship between genotype and phenotype.Methods All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNAgene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and thePCR products were screened for gene mutation by direct sequencing.Results Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patientssuffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2patients. The pattern of inheritance was autosomal dominant. Mutation c.73C>G (R25G) in exon 1 encoding the globulardomains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).Conclusions The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype ofmalignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletalmuscle dystrophy should be screened by genetic testing for the LMNA gene.