Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.

Background Cardiac conduction disease (CCD) is a common cardiovascular disease which can lead to life-threatening conditions. The importance of heredity in CCD has been realized in recent years. Several causal genes have been found to be implicated in CCD such asSCN5A,TRPM4,SCN1B,TNNI3K,LMNA, and NKX2.5. To date, only four genetic mutations inTNNI3Khave been identified related to CCD. Methods Whole-exome sequencing (WES) was carried out in order to identify the underlying disease-causing mutation in a Chinese family with CCD. The potential mutations were confirmed by Sanger sequencing. Real-time qPCR was used to detect the level ofTNNI3KmRNA expression. Results A nonsense mutation inTNNI3K(NM_015978.2: g.170891C > T, c.1441C > T) was identified in this family and validated by Sanger sequencing. Real-time qPCR confirmed that the level ofTNNI3KmRNA expression was decreased compared with the controls. Conclusions This study found the first nonsenseTNNI3Kmutation associated with CCD in a Chinese family.TNNI3Kharboring the mutation (c.1441C > T) implicated a loss-of-function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum ofTNNI3Kmutations, casting a new light upon the genotype-phenotype correlations betweenTNNI3K mutations and CCD and indicating the importance ofTNNI3Kscreening in CCD patients.