De novo variants identified by trio whole exome sequencing of bladder exstrophy epispadias complex.

Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE

Publication: Hoboken, N.J. : Wiley-Blackwell
Original Publication: Hoboken, N.J. : Wiley-Liss, c2003-

Bladder Exstrophy*/genetics ; Bladder Exstrophy*/pathology ; Epispadias*/genetics ; Epispadias*/pathology ; Anus, Imperforate* ; Hernia, Umbilical* ; Scoliosis* ; Urogenital Abnormalities*; Pregnancy ; Female ; Humans ; Animals ; Mice ; Exome Sequencing ; Urinary Bladder/pathology ; Transcription Factors/genetics ; Homeodomain Proteins/genetics

Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele-bladder exstrophy-imperforate anus-spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi-etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. MNX1 has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms "bladder exstrophy" in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi-etiological nature of BEEC.
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K23 DK119949 United States DK NIDDK NIH HHS; UM1 HG006542 United States HG NHGRI NIH HHS; L30 DK125951 United States DK NIDDK NIH HHS; 5K23DK119949-02 United States NH NIH HHS; 5UM1HG006542-08 United States NH NIH HHS

Keywords: bladder exstrophy; cloacal exstrophy; de novo; genetics; human; whole exome sequencing

0 (MNX1 protein, human)
0 (Transcription Factors)
0 (Homeodomain Proteins)

Bladder Exstrophy and Epispadias Complex; Omphalocele exstrophy imperforate anus

Date Created: 20231212 Date Completed: 20240311 Latest Revision: 20240812

20240813

PMC10939865

10.1002/ajmg.a.63501

38082334