TY - JOUR

T1 - Copy number variants suggest different molecular pathways for the pathogenesis of bladder exstrophy

AU - Nordenskjöld, Agneta

AU - Arkani, Samara

AU - Pettersson, Maria

AU - Winberg, Johanna

AU - Cao, Jia

AU - Fossum, Magdalena

AU - Anderberg, Magnus

AU - Barker, Gillian

AU - Holmdahl, Gundela

AU - Lundin, Johanna

N1 - Publisher Copyright: © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - bladder exstrophy

KW - chromosome

KW - CMA

KW - genetic

UR - http://www.scopus.com/inward/record.url?scp=85141564972&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.63031

DO - 10.1002/ajmg.a.63031

M3 - Journal article

C2 - 36349425

AN - SCOPUS:85141564972

VL - 191

SP - 378

EP - 390

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 2

ER -