A de novo mutation of SMYD1 (p.F272L) is responsible for hypertrophic cardiomyopathy in a Chinese patient

Abstract Background Hypertrophic cardiomyopathy (HCM) is a serious disorder and one of the leading causes of mortality worldwide. HCM is characterized as left ventricular hypertrophy in the absence of any other loading conditions. In previous studies, mutations in at least 50 genes have been identified in HCM patients. Methods In this research, the genetic lesion of an HCM patient was identified by whole exome sequencing. Real-time polymerase chain reaction (PCR), immunofluorescence and Western blot were used to analyze the effects of the identified mutation. Results According to whole exome sequencing, we identified a de novo mutation (c.814T>C/p.F272L) of SET and MYND domain containing histone methyltransferase 1 ( SMYD1 ) in a Chinese patient with HCM exhibiting syncope. We then generated HIS- SMYD1 -pcDNA3.1+ (WT and c.814T>C/p.F272L) plasmids for transfection into AC16 cells to functionalize the mutation. The immunofluorescence experiments indicated that this mutation may block the SMYD1 protein from entering the nucleus. Both Western blot and real-time PCR revealed that, compared with cells transfected with WT plasmids, the expression of HCM-associated genes such as β-myosin heavy chains, SMYD1 chaperones (HSP90) and downstream targets including TGF-β were all disrupted in cells transfected with the mutant plasmid. Previous studies have demonstrated that SMYD1 plays a crucial role in sarcomere organization and heart development. Conclusions This novel mutation (c.814T>C/p.F272L) may be the first identified disease-causing mutation of SMYD1 in HCM patients worldwide. Our research expands the spectrum of HCM-causing genes and contributes to genetic counseling for HCM patients.