Koellges, Ricarda and Stegmann, Jil and Schneider, Sophia and Waffenschmidt, Lea and Fazaal, Julia and Breuer, Katinka and Hilger, Alina C. and Dworschak, Gabriel C. and Mingardo, Enrico and Roesch, Wolfgang and Hofmann, Aybike and Neissner, Claudia and Ebert, Anne-Karolin and Stein, Raimund and Younsi, Nina and Hirsch-Koch, Karin and Schmiedeke, Eberhard and Zwink, Nadine and Jenetzky, Ekkehart and Thiele, Holger and Ludwig, Kerstin U. and Reutter, Heiko (2023) Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates <i>LZTR1</i> in Disease Formation. BIOMOLECULES, 13 (7): 1117. ISSN , 2218-273X
Full text not available from this repository. (Request a copy)Abstract
Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Methods: Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. Results: The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). Conclusions: According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLASSIC BLADDER EXSTROPHY; DATABASE; COMPLEX; CLOACA; exome analysis; molecular inversion probe; exstrophy; cloacal exstrophy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Apr 2024 13:09 |
| Last Modified: | 16 Apr 2024 14:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60755 |
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