[HTML][HTML] Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India
BMC medical genetics, 2018•Springer
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 …
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 …
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.
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