OBJECTIVETo explore the genotype-phenotype correlation of a MYH7-D554Y mutation identified in an ethnic Han Chinese pedigree affected with hypertrophic cardiomyopathy.

METHODSNinety six cardiovascular disease-related genes were detected in the proband by exonic amplification and high-throughput sequencing. Suspected mutations were verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. The pathogenicity and conservation of the detected mutations were analyzed with ClustalX, MutationTaster, PolyPhen-2, Provean and SIFT software.

RESULTSFour of the 5 first-degree relatives of the proband were diagnosed with hypertrophic cardiomyopathy. The proband has featured extremely hypertrophic left ventricular wall with a maximal thickness of 35 mm. Genetic testing showed that four of them have carried a heterozygous c.1660G>T (p.Asp554Tyr) mutation of the MYH7 gene, who the remaining one was phenotypically normal and did not carry the mutation. The mutation has not been recorded by the Human Gene Mutation Database (HGMD) and other databases. Bioinformatics analysis suggested that the mutation site is highly conserved and that the mutation is pathogenic.

CONCLUSIONThe p.Asp554Tyr mutation of the MYH7 gene probably underlies the hypertrophic cardiomyopathy in this pedigree.