{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T15:25:33Z","timestamp":1782833133574,"version":"3.54.5"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Inherited kidney diseases (IKDs) are a group of kidney diseases characterized by abnormal kidney structure or function caused by genetic factors, but they are not easily diagnosed in childhood due to either nonspecific symptoms and signs or clinically silent symptoms in the early stages until the progressive stages, even end-stages. Early diagnosis of IKDs is very urgent for timely treatment and improving outcomes of patients. So far, the etiological diagnosis has been accelerated with the advance of clinical genetic technology, particularly the advent of next-generation sequencing (NGS) that is not only a powerful tool for prompt and accurate diagnosis of IKDs but also gives therapy guidance to decrease the risk of unnecessary and harmful interventions.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The patients presenting with urinalysis abnormalities or structural abnormalities from 149 Chinese families were enrolled in this study. The clinical features of the patients were collected, and the potentially causative gene variants were detected using exome sequencing. The clinical diagnostic utility of the genetic testing was assessed after more detailed clinical data were analyzed.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> In total, 55 patients identified having causative variants by exome sequencing were genetically diagnosed, encompassing 16 (29.1%) autosomal dominant IKDs, 16 (29.1%) autosomal recessive IKDs, and 23 (41.8%) X-linked IKDs, with 25 unreported and 45 reported variants. The diagnostic yield was 36.9%. The utility of the exome sequencing was accessed, 12 patients (21.8%) were confirmed to have suspected IKDs, 26 patients (47.3%) discerned the specific sub-types of clinical category, and 17 patients (30.9%) with unknown etiology or lack of typical manifestations were reclassified.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our study supported that genetic testing plays a crucial role in the early diagnosis for children with IKDs, which affected follow-up treatment and prognostic assessment in clinical practice. Moreover, the variant spectrum associated with IKDs was expanded.<\/jats:p>","DOI":"10.3389\/fgene.2022.933636","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T19:24:46Z","timestamp":1673033086000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Diagnostic application of exome sequencing in Chinese children with suspected inherited kidney diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Min","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiang","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongtao","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.ekir.2021.10.012","article-title":"Last nucleotide substitutions of COL4A5 exons cause aberrant splicing","volume":"7","author":"Aoto","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1126\/science.2349482","article-title":"Identification of mutations in the COL4A5 collagen gene in Alport syndrome","volume":"248","author":"Barker","year":"1990","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.1007\/s00467-021-05141-5","article-title":"Diagnostic and clinical utility of genetic testing in children with kidney failure","volume":"36","author":"Chen","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1590\/2175-8239-JBN-2018-0217","article-title":"Rare inherited kidney diseases: An evolving field in Nephrology","volume":"42","author":"Cunha","year":"2020","journal-title":"J. Bras. Nefrol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.3389\/fgene.2019.01264","article-title":"Diagnostic yield of next-generation sequencing in patients with chronic kidney disease of unknown etiology","volume":"10","author":"De Haan","year":"2019","journal-title":"Front. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"100435","DOI":"10.1016\/j.xkme.2022.100435","article-title":"Emerging role of clinical genetics in CKD","volume":"4","author":"Devarajan","year":"2022","journal-title":"Kidney Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1016\/S0140-6736(14)60659-0","article-title":"Board of the working group for inherited kidney diseases of the European RenalRare inherited kidney diseases: Challenges, opportunities, and perspectives","volume":"383","author":"Devuyst","year":"2014","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1056\/NEJMoa1806891","article-title":"Diagnostic utility of exome sequencing for kidney disease","volume":"380","author":"Groopman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"354","DOI":"10.2215\/CJN.05750515","article-title":"The native kidney biopsy: Update and evidence for best practice","volume":"11","author":"Hogan","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1053\/j.ajkd.2020.03.026","article-title":"Alport syndrome: Achieving early diagnosis and treatment","volume":"77","author":"Kashtan","year":"2021","journal-title":"Am. J. Kidney Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1093\/ndt\/gfab218","article-title":"Genetic testing in the diagnosis of chronic kidney disease: Recommendations for clinical practice","volume":"37","author":"Knoers","year":"2022","journal-title":"Nephrol. Dial. Transpl."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1007\/s00467-012-2356-9","article-title":"The renal biopsy in the genomic era","volume":"28","author":"Liapis","year":"2013","journal-title":"Pediatr. Nephrol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1093\/ndt\/gfaa176","article-title":"Integration of genetic and histopathology data in interpretation of kidney disease","volume":"35","author":"Murray","year":"2020","journal-title":"Nephrol. Dial. Transpl."},{"key":"B14","doi-asserted-by":"publisher","first-page":"402","DOI":"10.23876\/j.krcp.20.111","article-title":"Genetic background, recent advances in molecular biology, and development of novel therapy in Alport syndrome","volume":"39","author":"Nozu","year":"2020","journal-title":"Kidney Res. Clin. Pract."},{"key":"B15","doi-asserted-by":"publisher","first-page":"100415","DOI":"10.1016\/j.xkme.2022.100415","article-title":"Polycystic kidney disease-related disease burden in adolescents with autosomal dominant polycystic kidney disease: An international qualitative study","volume":"4","author":"Oberdhan","year":"2022","journal-title":"Kidney Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/cge.13869","article-title":"Clinical application of a phenotype-based NGS panel for differential diagnosis of inherited kidney disease and beyond","volume":"99","author":"Oh","year":"2021","journal-title":"Clin. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1093\/ckj\/sfab056","article-title":"Genetic kidney diseases as an underrecognized cause of chronic kidney disease: The key role of international registry reports","volume":"14","author":"Torra","year":"2021","journal-title":"Clin. Kidney J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-981-10-5717-5_2","article-title":"Genetic test, risk prediction, and counseling","volume":"1005","author":"Wang","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"873","DOI":"10.34067\/KID.0006902020","article-title":"Whole-exome sequencing application for genetic diagnosis of kidney diseases: A study from southwest of Iran","volume":"2","author":"Zamani","year":"2021","journal-title":"Kidney360"},{"key":"B20","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1159\/000519095","article-title":"Next-generation sequencing-based genetic diagnostic strategies of inherited kidney diseases","volume":"7","author":"Zhang","year":"2021","journal-title":"Kidney Dis. (Basel)"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.933636\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T19:24:47Z","timestamp":1673033087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.933636\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":20,"alternative-id":["10.3389\/fgene.2022.933636"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.933636","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]},"article-number":"933636"}}