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

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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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Medical Genetics, Part A
Vol/bind191
Udgave nummer2
Sider (fra-til)378-390
Antal sider13
ISSN1552-4825
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
First, we would like to thank all participating families. We also thank Christina Clementson Kockum who was highly involved in the start of the study and Christina Nyström for technical assistance during the years of collecting DNA samples. The authors would like to acknowledge support from Science for Life Laboratory, the National Genomics Infrastructure, NGI, and Uppmax for providing assistance in massive parallel sequencing and computational infrastructure on fetal expression data.

Funding Information:
Swedish Research Council (grant K2012‐64X‐14506‐10‐5 2016–01642, to Agneta Nordenskjöld), Foundation Frimurare Barnhuset Stockholm, Stockholm City Council, Karolinska Institutet, the Swedish Brain Foundation, the Harald and Greta Janssons Foundation, and Erik Rönnbergs Foundation.

Funding Information:
Swedish Research Council, Grant/Award Number: K2012‐64X‐14506‐10‐5 2016–01642; Foundation Frimurare Barnhuset Stockholm; Stockholm City Council; Karolinska Institutet; the Swedish Brain Foundation; the Harald and Greta Janssons Foundation; Erik Rönnbergs Foundation Funding information

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

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