Mutation in δ-Sg Gene in Familial Dilated Cardiomyopathy

Asadi, Marzieh; Foo, Roger; Salehi, Ahmad Reza; Salehi, Rasoul; Samienasab, Mohammad Reza

Mutation in δ-Sg Gene in Familial Dilated Cardiomyopathy

Document Type : Original Article

Authors

¹ Endocrinology and Metabolism Research Center, School of Medicine, Arak University of Medical Sciences, Arak, Iran

² Cardiovascular Research Institute, Genome Institute of Singapore, Singapore

³ Department of Genetic and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences; Gerfa Namayesh Azmayesh (GENAZMA) Research Institute, Isfahan, Iran

⁴ Department of Cardiovascular Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

Abstract

Background: Mutations in different genes including dystrophin-associated glycoprotein complex caused familial dilated cardiomyopathy which is a genetically heterogeneous disease. The δ-SG gene contains nine exons spanning a 433-kb region of genomic DNA. It encodes a 35-kDa, singlepass, and type II transmembrane glycoprotein. Materials and Methods: In this study for the first time in Iran we screened 6 patients of a large family that they had positive family history of MI or sudden death by next generation sequencing method. Results: By employing NGS method we found missense mutation (p.R97Q) of δ-SG gene in 2 of 6 patients. Conclusions: The missense mutation (p.R97Q) in familial DCM patients is reported for the first time in Iranian patients with cardiac disease. Although this mutation is already known in other populations in Iran, it is not reported before.

Keywords

References

1.	Rutschow D, Bauer R, Göhringer C, Bekeredjian R, Schinkel S, Straub V, et al. S151A d-sarcoglycan mutation causes a mild phenotype of cardiomyopathy in mice. Eur J Hum Genet 2014;22:119-25.
2.	Yoshida T, Pan Y, Hanada H, Iwata Y, Shigekawa M. Bidirectional signaling between sarcoglycans and the integrin adhesion system in cultured L6 myocytes. J Biol Chem 1998;273:1583-90.
3.	Goehringer C, Rutschow D, Bauer R, Schinkel S, Weichenhan D, Bekeredjian R, et al. Prevention of cardiomyopathy in d-sarcoglycan knockout mice after systemic transfer of targeted adenoassociated viral vectors. Cardiovasc Res 2009;82:404-10.
4.	Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature 1992;355:696-702.
5.	Tsubata S, Bowles KR, Vatta M, Zintz C, Titus J, Muhonen L, et al. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J Clin Invest 2000;106:655-62.
6.	Manolio TA, Baughman KL, Rodeheffer R, Pearson TA, Bristow JD, Michels VV, et al. Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop). Am J Cardiol 1992;69:1458-66.
7.	Codd MB, Sugrue DD, Gersh BJ, Melton LJ 3^rd. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975-1984. Circulation 1989;80:564-72.
8.	Blain AM, Straub VW. δ-sarcoglycan-deficient muscular dystrophy: From discovery to therapeutic approaches. Skelet Muscle 2011;1:13-8.

Advanced Biomedical Research