Human Biology Review (ISSN 227 7 4424) 5 (4) 2016 ©Human Biology Review Original scientific paper (Das et al. pp. 422-436) www.humanbiologyjournal.com Revised and Accepted on September 14, 2016 422 Evaluating intra-genetic variants within exons 3 and 4 of LMNA in Dilated Cardiomyopathy patients from North India S. Das 1 , M. Kapoor 2 , J. Sanyal 3 , A. Biswas 4 , S. Seth 5 , B. Bhargava 6 and V.R. Rao 7 Citation: Das S, Kapoor M, Sanyal J, Biswas A, Seth S, Bhargava B and Rao VR. 2016. Evaluating intra-genetic variants within exons 3 and 4 of LMNA in Dilated Cardiomyopathy patients from North India. Human Biology Review, 5 (4), 422-436. 1 Soumi Das, Department of Anthropology, University of Delhi, Delhi-110007, INDIA, E mail: soumidas05@gmail.com , 2 Mitali Kapoor, Department of Anthropology, University of Delhi, Delhi-110007, INDIA, E mail: kapoormitali1989@gmail.com 3 Jaya Sanyal, Department of Anthropology, University of Delhi, Delhi-110007, INDIA, E mail: jayazoology@gmail.com 4 Amitabh Biswas, Department of Anthropology, University of Delhi, Delhi-110007, INDIA, E mail: amitabhbsws@gmail.com 5 Sandeep Seth , Department of Cardiology, All India Institute of Medical Sciences, New Delhi, INDIA, E mail: drsandeepseth@hotmail.com 6 Balram Bhargava , Department of Cardiology, All India Institute of Medical Sciences, New Delhi, INDIA, E mail: balrambhargava@yahoo.com 7 V.R. Rao, Department of Anthropology, University of Delhi, Delhi-110007, INDIA, E mail: profvrrao@gmail.com Corresponding author: Vadlamudi Raghavendra Rao, Department of Anthropology, University of Delhi, Delhi-110007, INDIA E mail: profvrrao@gmail.com ABSTRACT Mutations in LMNA are one of the causative factors to precipitate Dilated Cardiomyopathy (DCM), although the frequency of rare mutations segregating in familial cases has not been examined till date. Clinical cardiovascular data, family histories and blood samples were collected from 191 individuals (100 DCM cases and 91 controls). DNA samples were sequenced for nucleotide alterations in exons 3 and 4 for LMNA gene. Affected male-female sex ratio was 2:1 with 64.44% DCM males. Regular smokers among DCM patients were 79%. New York Heart Association classification showed that the number of females (n=14) affected by the disease was significantly more than that of males (n=12) only in NYHA classification III group (P=0.03) whereas number of males (n=14) were higher in NYHA IV when compared to females (n=3). There was a higher intake of polyunsaturated fatty acids as 59% of DCM patients were on non-vegetarian diet. A novel transversion mutation (c.639+1 G>C) was identified in the donor splice site region of intron 3 of LMNA gene in a male proband aged 45 years with severe disease course. Screening of family members revealed segregation in the family with son being affected with the same mutation and manifesting similar clinical symptoms, whereas absent from other individuals; thus similar phenotype with respect to a specific mutation in LMNA mutation carriers are observed. Novel exons 3 and 4 of LMNA contributed in the affected patient by creating a new cryptic donor splice site acting as a private mutation specific to a family. Social life style, heredity (family history positive) and male sex hormones play a role in disease causation, affecting characteristics as body fat distribution, which is associated with an increased risk of heart disease. The study revealed male preponderance accompanied by smoking habits, with middle-aged men being affected preferably, while a majority of female patients depicted greater severity of disease. Key words: Dilated Cardiomyopathy, LMNA, Private variant, splice-site mutation