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
{"title":"CAKUT个体的三重奏外显子组测序在19.62中发现了潜在的新候选基因的从头变异。","authors":"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","doi":"10.1016/j.gim.2025.101432","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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. Hence, this study aimed to identify potential novel CAKUT disease genes with de novo variants.</p><p><strong>Methods: </strong>We performed trio-based exome sequencing (ES) in 209 families with CAKUT to detect novel candidate disease genes.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":" ","pages":"101432"},"PeriodicalIF":6.6000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Trio exome sequencing in individuals with CAKUT identifies de novo variants in potential novel candidate genes in 19.62.\",\"authors\":\"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\",\"doi\":\"10.1016/j.gim.2025.101432\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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. Hence, this study aimed to identify potential novel CAKUT disease genes with de novo variants.</p><p><strong>Methods: </strong>We performed trio-based exome sequencing (ES) in 209 families with CAKUT to detect novel candidate disease genes.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12717,\"journal\":{\"name\":\"Genetics in Medicine\",\"volume\":\" \",\"pages\":\"101432\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.gim.2025.101432\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.gim.2025.101432","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Trio exome sequencing in individuals with CAKUT identifies de novo variants in potential novel candidate genes in 19.62.
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. Hence, this study aimed to identify potential novel CAKUT disease genes with de novo variants.
Methods: We performed trio-based exome sequencing (ES) 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.
期刊介绍：
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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