22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment

Area of Science:

• Genetics
• Developmental Biology
• Urology

Background:

• Bladder exstrophy is a congenital condition affecting bladder and urethral development, with an unknown genetic cause.
• Chromosomal aberrations are known to cause organ development defects, and some bladder exstrophy patients exhibit these.
• The 22q11.2 region is associated with genomic disorders; microduplications here present a variable phenotype.

Observation:

• Array-CGH analysis was performed on 36 Swedish bladder exstrophy patients.
• Two unrelated patients with bladder exstrophy and hearing impairment showed a similar ~3 Mb duplication in the 22q11.2 region.
• This duplication was confirmed by MLPA and FISH; subsequent analyses found no other deletions/duplications in this region among patients.

Findings:

• A 22q11.2 microduplication was identified in two patients with bladder exstrophy and hearing impairment.
• This finding represents the first reported association between 22q11.2 microduplication and this specific combination of conditions.
• One control individual also carried the microduplication, underscoring the variable expressivity of 22q11.2 microduplication syndrome.

Implications:

• The 22q11.2 microduplication may be a contributing genetic factor in some cases of bladder exstrophy, particularly when hearing impairment is present.
• This discovery expands the known phenotypic spectrum associated with 22q11.2 microduplication.
• Further research is warranted to elucidate the precise role of 22q11.2 duplications in congenital malformations and their variable clinical presentations.