Elsevier

Kidney International

Volume 61, Issue 4, April 2002, Pages 1243-1251
Kidney International

Genetic disorders – Development
Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1β mutations

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Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1β mutations.

Background

Renal tract malformations are, on occasion, associated with uterine malformations. The transcription factor hepatocyte nuclear factor (HNF)-1β is expressed from the earliest stages of development of the Wolffian duct, the mesonephros and metanephros, and the Müllerian ducts in the mouse. In adult mice HNF-1β is expressed in the kidney tubules, collecting ducts, and in the oviducts and uterus in the female (Müllerian duct derivatives) and in the epididymis, vas deferens and seminal vesicles (Wolffian duct derivatives) in the male. HNF-1β 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-1β 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-1β 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 proband'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-1β mutations and renal and Müllerian anomalies. The hypospadias may be coincidental. This study describes the first HNF-1β 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-1β mutations.

Keywords

genital malformation
transcription factors
HNF-1β mutation
hypospadia
renal tract malformation
heredity
Müllerian duct abnormality
urogenital adysplasia

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