22q11.2 duplications in a UK cohort with bladder exstrophy-epispadias complex

Area of Science:

• Genetics
• Developmental Biology
• Pediatric Urology

Background:

• The bladder exstrophy-epispadias complex (BEEC) is a spectrum of anterior midline defects affecting the genitourinary tract and bony pelvis.
• The exact cause of BEEC is unknown, but chromosomal abnormalities have been implicated.
• Previous reports identified 22q11.2 duplications in individuals with BEEC.

Purpose of the Study:

• To identify chromosomal copy number variants in patients with BEEC.
• To investigate the association between 22q11.2 duplications and BEEC.
• To explore the role of the CRKL gene in BEEC pathogenesis.

Main Methods:

• Genome-wide SNP6.0 microarray analysis was performed on 92 unrelated BEEC patients.
• A control group of 12,500 individuals with developmental delay was used for comparison.
• Sequencing of the CRKL gene was conducted in BEEC patients without 22q11.2 duplications.

Main Results:

• Three individuals with BEEC had a 22q11.2 duplication, a statistically significant finding compared to controls (p < .0001).
• No pathogenic variants in the CRKL gene were found in BEEC patients lacking 22q11.2 duplications.
• 22q11.2 duplication emerged as the most frequently identified genetic variant in BEEC.

Conclusions:

• 22q11.2 duplication is the genetic variant most commonly associated with BEEC.
• This supports the hypothesis that altered expression of a gene within the 22q11.2 region is critical for BEEC development.
• Further research is needed to identify the specific gene(s) involved.