Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease and dilated cardiomyopathy

Abstract

Background Cardiac conduction disease(CCD) and dilated cardiomyopathy(DCM) are two common cardiovascular diseases which can lead to life-threatening conditions. The importance of heredity in these two diseases has been realized in recent years. Several casual genes have been found to be implicated in CCD and DCM such as LMNA,SCN5A,TTN,TNNI3K and so on. Rare genetic mutations in TNNI3K have been identified to be in connection with CCD and DCM.Methods Next generation sequencing(NGS) was carried out in order to identify the underlying disease-causing mutation in a Chinese family with CCD and DCM. The mutations were validated by Sanger sequencing.Results A nonsense mutation in TNNI3K(NM_015978.2: g.170891C>T,c.1441C>T) was identified in this family and validated by Sanger sequencing.Conclusions This study described a Chinese family with CCD and DCM caused by a nonsense TNNI3K mutation.TNNI3K harboring the mutation(c.1441C>T) possibly implicated a loss-of-function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype-phenotype correlations between TNNI3K mutations and cardiovascular diseases.

Induced Mutation to Enhance Plant Biodiversity and Genetic Resources for Intensification of Crop Production to Mitigate Climatic Changes

“…Resistance to stem rot (Sclerotinia sclerotiorum) Rapeseed [60] Resistance to Ascochyta blight and Fusarium wilt Chickpea [61] Resistance to black stem rust Durum wheat [31] Resistance to stripe rust Wheat [31] Resistance to blast, yellow mottle virus, bacterial leaf blight, and bacterial leaf stripe Rice [31] Resistance to Myrothecium leaf spot and yellow mosaic virus Soybean [31] Resistance to bacterial blight, cotton leaf curl virus Cotton [62] Phytophthora nicotiana var. parasitica Sesame [63] Resistance against pathogen striga (Striga asiatica) Maize [64] Table 3.…”

Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

“…Previous studies have revealed that the Tnni3k locus on mouse chromosome 3 is related to cardiac survival, function, electrocardiographic PR‐interval 8,9 and viral myocarditis 10 . Human TNNI3K variants are related to cardiac disorders, including dilated cardiomyopathy, conduction disease and supraventricular arrhythmia 11–15 . Aberrant TNNI3K expression is observed in various cardiovascular diseases, such as myocardial hypertrophy, ischaemia/reperfusion injury and heart failure 16,17 .…”

“…10 Human TNNI3K variants are related to cardiac disorders, including dilated cardiomyopathy, conduction disease and supraventricular arrhythmia. [11][12][13][14][15] Aberrant TNNI3K ure. 16,17 Recent evidence has revealed that TNNI3K kinase activity is essential for maintaining normal cardiac physiology and that TNNI3K plays a crucial role in enhancing myocardial contractility.…”