Identification and Molecular Characterization of HNF1B Gene Mutations in Indian Diabetic Patients with Renal Abnormalities. (1st December 2014)

• Record Type: Journal Article
• Authors: Kanthimathi, Sekar; Balamurugan, Kandasamy; Mohan, Viswanathan; Shanthirani, Coimbatore Subramaniyam; Gayathri, Vijay; Radha, Venkatesan
• Is Part Of: Annals of human genetics. Volume 79:Number 1(2015:Jan.)
• Page Start: 10
• Page End: 19
• Publication Date: 2014-12-01
• Subjects: Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12093
• Languages: English
• ISSNs: 0003-4800

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Heterozygous mutations of the <italic>HNF1B</italic> gene (<italic>HNF1B</italic>‐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 <italic>HNF1B</italic> 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 <italic>HNF1B</italic> 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 <italic>HNF1B</italic> gene mutations which included four previously reported (<italic>‐67C>T</italic>, Arg165His, <italic>IVS2nt+2insT</italic>, Met1_Trp557del) and two novel variations (Asn321Asp, <italic>IVS3nt‐4C>G</italic>). 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 <italic>HNF1B‐</italic>MODY from India and shows that about 10% of young diabetic subjects with renal abnormalities seen at a tertiary diabetes centre harbor <italic>HNF1B</italic> gene mutations.</p> </abstract>