Genome-wide analysis for micro-aberrations in familial exstrophy of the bladder using array-based comparative genomic...

Area of Science:

• Urology
• Genetics
• Developmental Biology

Background:

• Bladder exstrophy (EB) is a rare congenital anomaly within the bladder-exstrophy-epispadias complex (BEEC).
• The etiology of BEEC is often attributed to exogenous factors due to its infrequent familial occurrence.
• This study investigates a potential genetic basis for BEEC in a consanguineous kindred with multiple affected members.

Observation:

• Three maternally related males from a Moroccan family presented with nonsyndromic classic bladder exstrophy.
• Affected individuals resided in different environments (Morocco and The Netherlands).
• One patient experienced long-term complications including scoliosis due to delayed surgical reconstruction.

Findings:

• Conventional karyotyping showed normal chromosomal structures in affected individuals.
• Array-based comparative genomic hybridization (array-CGH) identified a copy-number variant in the 1p21.1 region in both affected cousins.
• This variant encompassed the AMY1B, AMY2B, and AMY2A genes, which are involved in amylase production.

Implications:

• The identified copy-number variant is a known benign variant and likely unrelated to the bladder exstrophy phenotype.
• The familial occurrence of nonsyndromic bladder exstrophy in this kindred suggests a potential monogenic inheritance pattern.
• Further investigation is warranted to identify the specific genetic cause, possibly inherited in an autosomal-recessive or X-linked manner.