Mohan, V and Radha, V and Nguyen, T T and Stawiski, E W and Pahuja, K B and Goldstein, L D and Tom, Jennifer and Anjana, Ranjit Mohan and Kong-Beltran, Monica and Bhangale, T and Jahnavi, S and Chandni, Radhakrishnan and Gayathri, V and George, P and Zhang, Na and Murugan, Sakthivel and Phalke, Sameer and Chaudhuri, Subhra and Gupta, Ravi and Zhang, Jingli and Santhosh, Sam and Stinson, Jeremy and Modrusan, Zora and Ramprasad, V. L. and Seshagiri, Somasekar and Peterson, Andrew S. (2018) Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Medical Genetics, 19 (1). ISSN 1471-2350
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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.
Item Type: | Article |
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Official URL/DOI: | http://dx.doi.org/10.1186/s12881-018-0528-6 |
Uncontrolled Keywords: | Diabetes; Exome; Genomics analysis; MODY; NKX6–1 |
Subjects: | Genetics and Diabetes |
Divisions: | Department of Cell and Molecular Biology |
ID Code: | 1074 |
Deposited By: | surendar radha |
Deposited On: | 09 Mar 2018 12:09 |
Last Modified: | 09 Mar 2018 12:09 |
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