High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among Indians

BMC Medical Genetics

Research Article

Singh Priyamvada¹  Kumarasamy Thangaraj¹  Deepa Selvi Rani²  Lalji Singh³  Calambur Narasimhan⁴  Pratibha Nallari⁵ 

[1] Centre for Cellular and Molecular Biology, CSIR, Uppal Road, 500 007, Hyderabad, India;Centre for Cellular and Molecular Biology, CSIR, Uppal Road, 500 007, Hyderabad, India;Department of Genetics, Osmania University, Hyderabad, India;Centre for Cellular and Molecular Biology, CSIR, Uppal Road, 500 007, Hyderabad, India;Genome Foundation, Hyderabad, India;Banaras Hindu University, Varanasi, India;Department of Cardiology, CARE Hospitals, Hyderabad, India;Department of Genetics, Osmania University, Hyderabad, India;

关键词: TNNI3-;    Cardiomyopathy;    SNPs;    HCM;    Indians;    Mutations;   

DOI  :  10.1186/1471-2350-13-69

 received in 2012-03-17, accepted in 2012-08-01,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTroponin I (TNNI3) is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in hypertrophic cardiomyopathy patients (HCM). However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study.MethodsWe have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls, inhabited in the same geographical region of southern India.ResultsOur study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E) mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85%) with a rare codon (GAA: 14%). Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T) exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing.ConclusionOur study has provided valuable information regarding the prevalence of TNNI3 mutations in Indian HCM patients and its risk assessment, these will help in genetic counseling and to adopt appropriate treatment strategies.

【 授权许可】

Unknown   
© Rani et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.