Identification of a Novel LMNA Mutation in a Family with Dilated Cardiomyopathy and Sinus Bradycardia

Abstract

Background: Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, is characterized by left ventricular dilatation and systolic dysfunction. The aetiology of DCM remains unclear; however, accumulating evidence indicates that gene mutations account for some of the cases of DCM. Methods: Four affected female subjects from a three-generation Chinese family with DCM and sinus bradycardia are included in the present study; there were no affected male family members identified after cardiovascular examinations. The proband and her family members for genetic analysis and exome sequencing was used to analyze the exomes of two patients, II:5 and III:11. Results: The proband patient (II:5) was diagnosed with DCM and sinus bradycardia, the affected family member presented with sinus bradycardia and all were female, no male family members were affected. A heterozygous variant, c.T686C, p.I229T, in the LMNA gene was identified as the causative mutation in this family. Subsequently, this variant was verified in all family members by Sanger sequencing. No co-segregation of mutations was detected by mitochondrial sequencing of three affected female family members. Conclusions: To the best of our knowledge, the present study is the first report of sinus bradycardia in familial DCM patients with an LMNA mutation, as LMNA mutations are usually clinically associated with cardiac conduction disease. Therefore, our findings extend the mutation spectrum of the LMNA gene and have important implications for genetic counselling for the family.