D190Y mutation in C-terminal tail region of TNNI3 gene causing severe form of restrictive cardiomyopathy with mild hypertrophy in an Indian patient

Abstract Background Restrictive cardiomyopathy (RCM) is a rare condition with stiffening of the heart. Cardiac Troponin I gene is the most common causation of RCM constituting 8–10% of RCM cases and known responsible for either RCM with hypertrophy or hypertrophy with restrictive physiology. Methods Thirty RCM patients, 62 family members with 100 age, sex and ethnic matched subjects as controls were recruited from cardiology department of the All India Institute of Medical Sciences (AIIMS), New Delhi with written informed consent. 5 ml of blood sample was subjected to DNA extraction and all eight exons of the TNN13 gene were PCR amplified by 5 primer sets for Sanger sequencing. Results A rare heterozygous, de-novo missense mutation c.G568T p.D190Y is identified in a RCM patient having mild hypertrophy with restrictive physiology as it is absent in all unaffected family members, controls, other RCM patients of the study and several genome and exome data bases. This mutation is highly conserved and in-silico functional and protein structure analyses found it likely pathogenic. Conclusion In the present study, out of 30 RCM Indian patients screened for all 8 exons of the TNN13 gene, only one patient (3.33%) was found with the mutation. Variations and the substitution of different amino acids on same codons of TNN13 gene confer different range phenotypes. In summary, this study contributes to the mutation spectrum in exon 8 as hot spot region of the TNN13 gene causing RCM.