Deletion of Hepatocyte Nuclear Factor-1-Beta in an Infant with Prune Belly Syndrome

ABSTRACT

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-β gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-β microdeletion. Hepatocyte nuclear factor-1-β is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-β cause the “renal cysts and diabetes syndrome,” isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-β may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension.

KEYWORDS

Prune belly syndrome - Eagle-Barrett syndrome - Obrinsky syndrome - Fröhlich's syndrome - triad syndrome - chromosome 17q - CGH - HNF1B - vHnf1 - TCF2

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