Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy

• Published in: American journal of medical genetics. Part A Vol. 191; no. 2; pp. 378 - 390
• Main Authors: Nordenskjöld, Agneta, Arkani, Samara, Pettersson, Maria, Winberg, Johanna, Cao, Jia, Fossum, Magdalena, Anderberg, Magnus, Barker, Gillian, Holmdahl, Gundela, Lundin, Johanna
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-02-2023; Wiley Subscription Services, Inc
• Subjects: Bladder; bladder exstrophy; Bladder Exstrophy - genetics; Celsr3 protein; chromosome; Chromosome 22; Chromosome Aberrations; Chromosomes; Clinical Medicine; CMA; Congenital defects; Copy number; DNA Copy Number Variations - genetics; DNA microarrays; Genes; genetic; Golgi apparatus; Humans; Infant, Newborn; Islet-1 protein; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Original; Pathogenesis; Pediatrics; Pediatrik; Signal transduction; Urinary bladder; Urinary Bladder - abnormalities; Wnt protein; genetic; bladder exstrophy; CMA; chromosome
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63031

Bladder exstrophy is a rare congenital malformation leaving the urinary bladder open in the midline of the abdomen at birth. There is a clear genetic background with chromosome aberrations, but so far, no consistent findings apart from 22q11‐duplications detected in about 2%–3% of all patients. Some genes are implicated like the LZTR1, ISL1, CELSR3, and the WNT3 genes, but most are not explained molecularly. We have performed chromosomal microarray analysis on a cohort of 140 persons born with bladder exstrophy to look for submicroscopic chromosomal deletions and duplications. Pathogenic or possibly pathogenic microdeletions or duplications were found in 16 patients (11.4%) and further 9 with unknown significance. Two findings were in regions linked to known syndromes, two findings involved the same gene (MCC), and all other findings were unique. A closer analysis suggests a few gene networks that are involved in the pathogenesis of bladder exstrophy; the WNT‐signaling pathway, the chromosome 22q11 region, the RIT2 and POU families, and involvement of the Golgi apparatus. Bladder exstrophy is a rare malformation and is reported to be associated with several chromosome aberrations. Our data suggest involvement of some specific molecular pathways.