Rare exonic CELSR3 variants identified in Bladder Exstrophy Epispadias Complex.

Area of Science:

• Genetics
• Developmental Biology
• Urology

Background:

• Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly with an unknown cause, though genetic and environmental factors are implicated.
• Previous studies have identified gene variants in the urogenital pathway linked to bladder exstrophy.
• Advances in genomic sequencing offer new avenues for investigating the molecular underpinnings of BEEC.

Purpose of the Study:

• To identify rare heterozygous variants in genes previously associated with bladder exstrophy.
• To correlate these genetic variants with bladder regeneration capacity in patients with BEEC.

Main Methods:

• A case series of 12 patients with BEEC undergoing bladder biopsies was analyzed.
• Patients were classified based on bladder volume as
• sufficient
• or
• insufficient
• for regeneration.
• Whole exome sequencing was performed on bladder tissue DNA.
• Analysis focused on autosomal dominant variants in genes implicated in BEEC.

Main Results:

• A literature review identified 44 genes associated with human bladder exstrophy models.
• Rare variants were found in two implicated genes in
• sufficient
• regeneration cases.
• Seven variants in five implicated genes were identified in
• insufficient
• regeneration cases.

Conclusions:

• Rare variants in seven previously implicated genes were identified in BEEC specimens.
• Further research is necessary to elucidate the cellular signaling pathways involved in this genetically heterogeneous condition.
• Understanding the genetic basis of BEEC is crucial for advancing knowledge of bladder development and regeneration.