Hnf1b gene

The HNF1B gene is located on chromosome 17q12 and maps for the "Hepatocyte nuclear factor-1-beta" also called "Transcription factor-2", a transcription factor that is already expressed in the foetus in kidney, liver, bile ducts, thymus, genital tract, pancreas, lung and intestine.

The autosomal dominant monogenic mutation of the HNF1B gene leads to MODY5 ("Maturity-onset diabetes of the Young type 5"), a disease pattern from the group of autosomal-dominantly inherited, clinically heterogeneous, not always insulin-dependent forms of diabetes.

Several disease-causing germline mutations have been identified for the following diseases:

• Diabetes mellitus, noninsulin-dependent OMIM: 125853 (Furuta H et al.)
• Renal cysts and diabetes syndrome OMIM: 137920 (Bingham C et al. 2003)
• Renal cell carcinoma, chromophobic OMIM: 144700 (Rebouissou et al. 2005)
• CAKUT: Wakayama et al. (2010) identified heterozygous HNF1B mutations in 5 (10%) of 50 Japanese children with congenital anomalies of kidneys and urinary tract (CAKUT) partially combined with renal cysts.

1. Bingham C et al (2003) Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1-beta gene mutation. Kidney Int 63: 1645-1651
2. Furuta H et al (2002) Nonsense and missense mutations in the human hepatocyte nuclear factor-1-beta gene (TCF2) and their relation to type 2 diabetes in Japanese. J Clin Endocr Metab 87: 3859-3863
3. Wakayama M et al (2o10) HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatric nephrol 25:1073-1079
4. Lindner T et al (1999) A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1-beta. Hum Molec Genet 8: 2001-2008
5. Rebouissou S et al (2005) Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas. Hum Molec gene 14: 603-614