Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy. Issue 2 (8th November 2022)

• Record Type: Journal Article
• Authors: Nordenskjöld, Agneta; Arkani, Samara; Pettersson, Maria; Winberg, Johanna; Cao, Jia; Fossum, Magdalena; Anderberg, Magnus; Barker, Gillian; Holmdahl, Gundela; Lundin, Johanna
• Is Part Of: American journal of medical genetics. Volume 191:Issue 2(2023)
• Page Start: 378
• Page End: 390
• Publication Date: 2022-11-08
• Subjects: bladder exstrophy -- chromosome -- CMA -- genetic; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.63031
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: 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.