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Lookup NU author(s): Professor Judith Goodship, Professor Tim Goodship, Anne Hattersley
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Background. Renal tract malformations are, on occasion, associated with uterine malformations. The transcription factor hepatocyte nuclear factor (HNF)-1beta is expressed from the earliest stages of development of the Wolffian duct, the mesonephros and metanephros, and the Mullerian ducts in the mouse. In adult mice HNF-1beta is expressed in the kidney tubules, collecting ducts, and in the oviducts and uterus in the female (Mullerian duct derivatives) and in the epididymis, vas deferens and seminal vesicles (Wolffian duct derivatives) in the male. HNF-1beta mutations have been reported in two families where affected members have renal abnormalities, female genital tract malformations and early-onset diabetes. Renal and uterine abnormalities have not been described in families without early-onset diabetes. Methods. We sequenced the HNF-1beta gene in nine subjects with renal abnormalities and a personal or family history of female genital tract malformations, but no history of diabetes. Results. Two families were identified with novel HNF-1beta mutations: a missense mutation in exon 2 with conversion of serine to proline at codon 151 (S151P) and a frameshift mutation in exon 3 with a 1 base pair deletion at codon 243 (Q243fsdelC). The S151P mutation proband has cystic kidneys and uterus didelphys. Her affected second son has renal cysts and hypospadias. The Q243fsdelC proband has a single functioning kidney and her two children have renal dysplasia. Histology in one child shows cystic dysplasia with a lack of glomeruli. The pro-band's sister is a mutation carrier and has a bicornuate uterus. Diabetes is not a feature in either family. Conclusions. This study confirms an association between HNF-1beta mutations and renal and Mullerian anomalies. The hypospadias may be coincidental. This study describes the first HNF-1beta mutations that are associated with a single functioning kidney and the absence of diabetes. This study further reinforces the variability of the renal and non-renal phenotypes associated with HNF-1beta mutations.
Author(s): Bingham C, Ellard S, Cole TRP, Jones KE, Allen LIS, Goodship JA, Goodship THJ, Bakalinova-Pugh D, Russell GI, Woolf AS, Nicholls AJ, Hattersley AT
Publication type: Article
Publication status: Published
Journal: Kidney International
Year: 2002
Volume: 61
Issue: 4
Pages: 1243-1251
ISSN (print): 0085-2538
ISSN (electronic): 1523-1755
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1046/j.1523-1755.2002.00272.x
DOI: 10.1046/j.1523-1755.2002.00272.x
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