[A novel HAND1 mutation associated with sporadic dilated cardiomyopathy].

Objective: To investigate a novel mutation in the HAND1 gene associated with sporadic dilated cardiomyopathy (DCM). Methods: From February 2013 to February 2017, the clinical data and peripheral venous blood samples were collected from 120 patients with sporadic DCM and 200 healthy controls, who were both from the Fifth People's Hospital of Shanghai, Fudan University and Shanghai Chest Hospital, Shanghai Jiaotong University.The genomic DNA was extracted from the study participants.The coding exons of HAND1 were amplified from the study subjects by polymerase chain reaction, and were sequenced for a potential HAND1 mutation.The online computer programs MUSCLE and Mutation Taster were used to analyze the conversation of an altered amino acid and to predict the disease-causing potential of an identified mutation, respectively.The wild-type HAND1 was cloned and the mutant was generated by site-directed mutagenesis.The Dual-luciferase reporter assay kits were used to explore the functional characteristics of the mutant HAND1. Results: A novel heterozygous mutation, a substitution of thymine for guanine at nucleotide 346 (c.346G>T), predicting the conversion of a glutamic acid-encoding codon into a stop codon at codon 116 (p.E116X), was detected in a patient with sporadic DCM.The nonsense mutation was absent in the 200 control individuals.The altered glutamic acid at amino acid position 116 was highly conserved evolutionarily, and the mutation was predicted to be pathogenic.Biological analyses revealed that the mutant HAND1 lost the ability to transcriptionally activate a target gene. Conclusion: Loss-of-function mutation in HAND1 is likely to be an uncommon cause responsible for sporadic DCM.