Scientific background:

Summary: This transcription factor plays a key role in pancreatic beta cell function and kidney development, so mutations in HNF1B cause maturity-onset diabetes of the young type 5 (MODY5) and kidney abnormalities.

Clinical signs: Mutations of the transcription factor HNF1beta result in hereditary diabetes (MODY5), various urogenital malformations, and hypomagnesemia.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Montoli A et al. (2002) Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1 beta gene: description of a new family with associated liver involvement.
Bellanné-Chantelot C et al. (2005) Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5.
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.
Bingham C et al. (2002) Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1beta mutations.
Kolatsi-Joannou M et al. (2001) Hepatocyte nuclear factor-1beta: a new kindred with renal cysts and diabetes and gene expression in normal human development.
Adalat S et al. (2009) HNF1B mutations associate with hypomagnesemia and renal magnesium wasting.
Abbott C et al. (1990) Mapping of the gene TCF2 coding for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction.
Bach I et al. (1991) Two members of an HNF1 homeoprotein family are expressed in human liver.
Barbacci E et al. (2004) HNF1beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.
Bellanné-Chantelot C et al. (2004) Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations.
Bingham C et al. (2001) Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease.
Bingham C et al. (2000) Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1 beta.
Bingham C et al. (2003) Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation.
Carette C et al. (2007) Exonic duplication of the hepatocyte nuclear factor-1beta gene (transcription factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5.
Edghill EL et al. (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes.
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.
Gudmundsson J et al. (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
Harries LW et al. (2005) The position of premature termination codons in the hepatocyte nuclear factor -1 beta gene determines susceptibility to nonsense-mediated decay.
Hiesberger T et al. (2004) Mutation of hepatocyte nuclear factor-1beta inhibits Pkhd1 gene expression and produces renal cysts in mice.
Horikawa Y et al. (1997) Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY.
Iwasaki N et al. (2001) Splice site mutation in the hepatocyte nuclear factor-1 beta gene, IVS2nt + 1G > A, associated with maturity-onset diabetes of the young, renal dysplasia and bicornuate uterus.
Kaplan BS et al. (1989) Familial hypoplastic glomerulocystic kidney disease: a definite entity with dominant inheritance.
Kolatsi-Joannou M et al. (2001) Hepatocyte nuclear factor-1beta: a new kindred with renal cysts and diabetes and gene expression in normal human development.
Lindner TH 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-1beta.
Ma Z et al. (2007) Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.
Maestro MA et al. (2003) Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas.
Mefford HC et al. (2007) Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy.
Menzel R et al. (1998) A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene.
Nishigori H et al. (1998) Frameshift mutation, A263fsinsGG, in the hepatocyte nuclear factor-1beta gene associated with diabetes and renal dysfunction.
Rebouissou S et al. (2005) Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas.
Rizzoni G et al. (1982) Familial hypoplastic glomerulocystic kidney. A new entity?
Verdeguer F et al. (2010) A mitotic transcriptional switch in polycystic kidney disease.
Wild W et al. (2000) The mutated human gene encoding hepatocyte nuclear factor 1beta inhibits kidney formation in developing Xenopus embryos.
Yorifuji T et al. (2004) Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism.