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INTRODUCTION:
Prune belly syndrome (PBS) is a rare complex of abnormal abdominal wall musculature, urinary tract anomalies, and bilateral cryptorchidism, and is associated with significant morbidity. The cause of PBS is unknown, however a male predominance (95%) and identified families with multiple affected individuals suggests PBS may be an X-linked or sex-limited genetic disease. Disease-causing DNA changes can vary from chromosomal alterations detectable by karyotyping to point mutations detected by DNA sequencing. More recently discovered, copy-number variations (CNVs) are small deletions or duplications that affect the number of copies of a gene. CNVs are missed by DNA sequencing and karyotyping but have been shown to account for previously unexplained genetic diseases by identifying candidate genes or regions involved in various disorders. The purpose of this study was to assess if novel CNVs are present in PBS patients.
MATERIALS & METHODS:
From 2008-current, blood samples from PBS patients were prospectively tested by whole genome comparative genomic hybridization (CGH) using the array version current (V8.1 or V8.3) at the time of ascertainment (Baylor Medical Genetics Laboratory, Houston TX).  When possible, in cases wherein novel genomic CNVs were detected, parental testing (via FISH probes) was performed to identify whether CNVs are de novo or inherited.
RESULTS:
CGH testing on 12 PBS cases identified 5 (42%) patients with novel CNVs. Two patients have duplication CNVs: one patient has a maternally inherited 0.360Mb duplication on 2q11.2 and one patient has a 0.324Mb duplication on Xq23 of unknown genetic origin. Two patients have deletion CNVs: one patient has a paternally inherited 0.271Mb deletion on 7q31.1 and one patient has a maternally inherited 0.113Mb deletion on Xq22.1. Additionally, one adopted patient has two 0.066-0.151Mb deletions on 6q23.2 and 7q33.2 of unknown genetic origin.
CONCLUSIONS:
Prune belly syndrome (PBS) is a rare but morbid birth defect and novel CNVs are common in these males (42%). The finding that 2 of the 5 identified CNVs are located on chromosome X supports the hypothesis that PBS is an X-linked genetic disease. Further investigation of these genomic rearrangements may lead to the identification of genetic causes of PBS, thereby aiding prenatal diagnosis and genetic counseling.