ABSTRACT
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 HNF1B-MODY from India and shows that about 10% of young diabetic subjects with renal abnormalities seen at a tertiary diabetes centre harbor HNF1B gene mutations.
