Genome Sequencing in 19 Families With Bladder Exstrophy and Epispadias Complex Indicates Involvement of the ADGR-Gene Family.
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Nordenskjöld A, Alm S, Eisfeldt J, Cao J, Anderberg M, Barker G, Matsson H, Holmdahl G, Lindstrand A, Lagerstedt-Robinson K
Am. J. Med. Genet. A - (-) - [2026-02-10; online 2026-02-10]
Bladder exstrophy and epispadias complex (BEEC) is one of the most severe congenital malformations of the urogenital tract, significantly impacting continence, sexual function, and renal function. To date, the only recurrent genetic aberration identified is the 22q.11.2 microduplication, but several candidate regions and genes including components of the WNT signaling pathway have been proposed. This study aimed to identify additional genes contributing to the pathogenesis of BEEC and to verify previously suggested candidate genes. We performed trio-based whole genome sequencing on 19 individuals with BEEC and their unaffected parents; of those, five carried earlier reported microdeletions. The genome data was also filtered in silico for variants in 204 candidate genes selected from databases, publications, and in-house findings. Variants were prioritized based on allele frequency and predicted functional impact. In 8 of the 19 trios, our findings highlight members of the ADGR-gene family as novel candidate genes for BEEC, alongside other implicated genes such as TRANK1, CSNK1E, IFT122, SDK1, SDK2, and KIF19 and propose two more CNVs as risk factors for BEEC; on chromosome regions 1p36 and 16p11.2. This study identifies novel candidate genes for BEEC within the ADGR gene family. The results also further implicate a complex molecular background of BEEC.
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 41668247
DOI 10.1002/ajmga.70074
Crossref 10.1002/ajmga.70074