Identification and Molecular Characterization ofHNF1BGene Mutations in Indian Diabetic Patients with Renal Abnormalities

Kanthimathi, S and Balamurugan, K and Mohan, V and Shanthirani, C S and Gayathri, V and Radha, V (2014) Identification and Molecular Characterization ofHNF1BGene Mutations in Indian Diabetic Patients with Renal Abnormalities. Annals of Human Genetics, 79 (1). p. 10. ISSN 00034800

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Heterozygous mutations of the HNF1B gene (HNF1B-MODY or MODY5) are associated with a wide clinical spectrum of renal and extrarenal disease without clear genotype–phenotype correlation. In this study, we investigated the prevalence of HNF1B gene mutations in young Indian diabetic patients with various renal abnormalities. Fifty unrelated young diabetic patients, who also had renal abnormalities, were selected from the electronic records of a large diabetes centre in Chennai, in southern India. All patients were sequenced for HNF1B gene mutations. The whole or partial gene deletion was analyzed by MLPA. Functional characterization of the novel variant (Asn321Asp) was also performed using transcriptional activation and subcellular localization assays. We identified six different HNF1B gene mutations which included four previously reported (-67C>T, Arg165His, IVS2nt+2insT, Met1_Trp557del) and two novel variations (Asn321Asp, IVS3nt-4C>G). The functional study revealed that the novel variation Asn321Asp in both the heterozygous and homozygous state showed similar transcriptional activity, expression levels and normal transportation of protein to the nucleus similar to wild type, suggesting that it is not likely to be pathogenic. This is the first major study of HNF1BMODY from India and shows that about 10% of young diabetic subjects with renal abnormalities seen at a tertiary diabetes centre harbor HNF1B gene mutations.

Item Type:Article
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Uncontrolled Keywords:Asian Indians, autoantibody-negative type 1 diabetes, MLPA, MODY5, RCAD, renal cyst, South Asians
Subjects:Genetics and Diabetes > Maturity-Onset Diabetes of the Young(MODY)
Genetics and Diabetes
Divisions:Department of Cell and Molecular Biology
Department of Diabetology
ID Code:911
Deposited By:surendar radha
Deposited On:06 Jul 2015 12:01
Last Modified:06 Jul 2015 12:01

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