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Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families

Purpose - Congenital anomalies of the kidney and urinary tract (CAKUT) encompass heterogenous malformations arising from defective nephrogenesis. To date, approximately 50 monogenic genes are known to cause CAKUT if mutated. Recent studies show the impact of de novo variants in genetic disease etiol...

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Main Authors: Merz, Lea Maria (Author) , Kolvenbach, Caroline M. (Author) , Wang, Chunyan (Author) , Mertens, Nils David (Author) , Seltzsam, Steve (Author) , Mansour, Bshara (Author) , Zheng, Bixia (Author) , Schneider, Sophia (Author) , Schierbaum, Luca (Author) , Hölzel, Selina (Author) , Salmanullah, Daanya (Author) , Pantel, Dalia (Author) , Kalkar, Gina (Author) , Connaughton, Dervla M. (Author) , Mann, Nina (Author) , Wu, Chen-Han Wilfred (Author) , Kause, Franziska (Author) , Nakayama, Makiko (Author) , Dai, Rufeng (Author) , Schneider, Ronen (Author) , Buerger, Florian (Author) , Nicolas-Frank, Camille (Author) , Yousef, Kirollos (Author) , Lemberg, Katharina (Author) , Saida, Ken (Author) , Yu, Seyoung (Author) , Elmubarak, Izzeldin (Author) , Franken, Gijs A. C. (Author) , Lomjansook, Kraisoon (Author) , Braun, Alina (Author) , Bauer, Stuart B. (Author) , Rodig, Nancy M. (Author) , Somers, Michael J. G. (Author) , Traum, Avram Z. (Author) , Stein, Deborah R. (Author) , Daga, Ankana (Author) , Baum, Michelle A. (Author) , Daouk, Ghaleb H. (Author) , Awad, Hazem S. (Author) , Eid, Loai A. (Author) , El Desoky, Sherif (Author) , Shalaby, Mohammed A. (Author) , Kari, Jameela A. (Author) , Ooda, Said (Author) , Fathy, Hanan M. (Author) , Soliman, Neveen A. (Author) , Nabhan, Marwa (Author) , Abdelrahman, Safaa (Author) , Hilger, Alina C. (Author) , Mane, Shrikant M. (Author) , Ferguson, Michael A. (Author) , Tasic, Velibor (Author) , Shril, Shirlee (Author) , Hildebrandt, Friedhelm (Author)
Format: Article (Journal)
Language:English
Published: July 2025
In: Genetics in medicine
Year: 2025, Volume: 27, Issue: 7, Pages: 1-16
ISSN:1530-0366
DOI:10.1016/j.gim.2025.101432
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.gim.2025.101432
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1098360025000796
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Author Notes:Lea Maria Merz, Caroline M. Kolvenbach, Chunyan Wang, Nils David Mertens, Steve Seltzsam, Bshara Mansour, Bixia Zheng, Sophia Schneider, Luca Schierbaum, Selina Hölzel, Daanya Salmanullah, Dalia Pantel, Gina Kalkar, Dervla M. Connaughton, Nina Mann, Chen-Han Wilfred Wu, Franziska Kause, Makiko Nakayama, Rufeng Dai, Ronen Schneider, Florian Buerger, Camille Nicolas-Frank, Kirollos Yousef, Katharina Lemberg, Ken Saida, Seyoung Yu, Izzeldin Elmubarak, Gijs A. C. Franken, Kraisoon Lomjansook, Alina Braun, Stuart B. Bauer, Nancy M. Rodig, Michael J. G. Somers, Avram Z. Traum, Deborah R. Stein, Ankana Daga, Michelle A. Baum, Ghaleb H. Daouk, Hazem S. Awad, Loai A. Eid, Sherif El Desoky, Mohammed A. Shalaby, Jameela A. Kari, Said Ooda, Hanan M. Fathy, Neveen A. Soliman, Marwa Nabhan, Safaa Abdelrahman, Alina C. Hilger, Shrikant M. Mane, Michael A. Ferguson, Velibor Tasic, Shirlee Shril, Friedhelm Hildebrandt
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Summary:Purpose - Congenital anomalies of the kidney and urinary tract (CAKUT) encompass heterogenous malformations arising from defective nephrogenesis. To date, approximately 50 monogenic genes are known to cause CAKUT if mutated. Recent studies show the impact of de novo variants in genetic disease etiology. Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families. - Methods - We performed trio-based exome sequencing in 209 families with CAKUT to detect novel candidate disease genes. - Results - Trio analysis yielded in the identification of CAKUT candidate genes in 96 of 209 trio families (45.93%). In 41 of 209 cases, we detected strong de novo variants in 45 potential novel CAKUT candidate genes (19.62%). We developed a prioritization approach that highlights a truncating de novo variant in SOX13 (HGNC:11192) as a promising cause for CAKUT. In addition, further allele carriers for the candidate gene CHD1L (HGNC:1916) were identified, thus supporting the role of CHD1L in the pathogenesis of CAKUT. - Conclusion - We conclude that de novo variants in potential novel CAKUT candidate genes contribute to the disease etiology and present SOX13 as a potential novel cause for CAKUT.
Item Description:Online verfügbar: 11. April 2025, Artikelversion: 5. Juni 2025
Gesehen am 19.01.2026
Physical Description:Online Resource
ISSN:1530-0366
DOI:10.1016/j.gim.2025.101432

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