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


Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
02 2023
Historique:
revised: 05 08 2022
received: 04 07 2022
accepted: 07 10 2022
pubmed: 10 11 2022
medline: 13 1 2023
entrez: 9 11 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36349425
doi: 10.1002/ajmg.a.63031
pmc: PMC10100507
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

378-390

Informations de copyright

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

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Auteurs

Agneta Nordenskjöld (A)

Department of Women's and Children's Health, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Pediatric Surgery, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden.

Samara Arkani (S)

Department of Women's and Children's Health, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Urology, Danderyds Hospital, Danderyd, Sweden.

Maria Pettersson (M)

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Johanna Winberg (J)

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Jia Cao (J)

Department of Women's and Children's Health, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Magdalena Fossum (M)

Department of Women's and Children's Health, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Pediatric Surgery, Copenhagen University, Righospitalet, København, Denmark.

Magnus Anderberg (M)

Department of Pediatric Surgery, Skåne University Hospital, Lund, Sweden.
Department of Clinical Sciences, Lund University, Lund, Sweden.

Gillian Barker (G)

Department of Pediatric Surgery, Uppsala Academic Hospital, Uppsala, Sweden.

Gundela Holmdahl (G)

Department of Women's and Children's Health, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Pediatric Surgery, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden.
Sahlgrenska Academy, Women's and Children's Health, Gothenburg, Sweden.
Department of Pediatric Surgery, Queen Silvia's Children's Hospital, Gothenburg, Sweden.

Johanna Lundin (J)

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

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Classifications MeSH