Genetic basis of prune belly syndrome: screening for HNF1? gene.
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ABSTRACT: PURPOSE:Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1? gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1? mutations. We assessed the role of HNF1? in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations. MATERIALS AND METHODS:We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1? gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1? to activate a luciferase construct with an HNF1? DNA binding site. RESULTS:From 32 prune belly syndrome probands (30 males, 2 females) HNF1? sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1?, suggesting the V61G substitution does not disturb HNF1? function. CONCLUSIONS:One genomic HNF1? mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1? mutations are uncommon in prune belly syndrome, despite case reports of HNF1? deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome.
SUBMITTER: Granberg CF
PROVIDER: S-EPMC3399512 | biostudies-literature | 2012 Jan
REPOSITORIES: biostudies-literature
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