Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India

BMC Medical Genetics

Jennifer Tom¹  Tushar Bhangale¹  Radhakrishnan Chandni²  Eric W. Stawiski³  Kanika Bajaj Pahuja³  Na Zhang³  Jingli Zhang³  Andrew S. Peterson³  Zora Modrusan³  Subhra Chaudhuri³  Monica Kong-Beltran³  Jeremy Stinson³  Thong T. Nguyen³  Leonard D. Goldstein³  Somasekar Seshagiri³  Ranjit Mohan Anjana⁴  Venkatesan Radha⁴  Viswanathan Mohan⁴  Vijay Gayathri⁴  Suresh Jahnavi⁴  Paul George⁵  Sameer Phalke⁵  Sakthivel Murugan⁵  Sam Santhosh⁵  V. L. Ramprasad⁵  Ravi Gupta⁵ 

[1] Department of Bioinformatics and Computational Biology, Genentech Inc.;Department of General Medicine, Govt. Medical College;Department of Molecular Biology, Genentech Inc.;Madras Diabetes Research Foundation & Dr. Mohan’s Diabetes Specialities Centre;MedGenome;

关键词: MODY;    Diabetes;    Exome;    Genomics analysis;    NKX6–1;   

DOI  :  10.1186/s12881-018-0528-6

来源: DOAJ

【 摘 要 】

Abstract Background Maturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. Methods In this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed. Results We found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6–1 that may contribute to development of MODY. Functional assessment of the NKX6–1 variants showed that they are functionally impaired. Conclusions Our findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6–1, and these require further validation.

【 授权许可】

Unknown