Novel mutations in LMNA A/C geneand associated phenotypes

摘要

Mutations in the lamin A/C gene (LMNA) have been associated with several phenotypes ranging from systemic to prevalent of muscle, heart, skin, nerve etc. More recently they have been associated with dilated cardiomyopathy (DCM) and severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). We report four novel mutations - 3 missense and 1 deletion – in 4 unrelated patients showing different phenotypes, ranging from the early onset congenital form of laminopathy to classical LGMD phenotype, to LGMD and heart involvement. All these newly identified variants were not found in 300 ethnicallymatched control subjects.The variant c.103-105del CTG was described post-mortem in a young patient with congenital muscular dystrophy who presented at the age of 9 a first degree A-V block and subsequently several episodes of supraventricular parossystic tachycardia. Two patients presented as onset symptom lower limbs muscle weakness, and developed heart conduction defects requiring pacemaker implantation at the age of 26 and 38 years, respectively. One of them who carried the mutation c.1339G>C died at the age of 40 by intractable heart failure; the second one carrying the mutation 265C>T died at the age of 30, for a trmboembolic event. A classical LGMD phenotype without heart involvement was observed in the patient with the mutation 1579C>T, who died at the age of 68 years for respiratory insufficiency.