{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:22Z","timestamp":1753892062839,"version":"3.41.2"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Whole exome sequencing (WES) technology has been increasingly used for the etiological diagnosis of fetuses with ultrasound anomalies. In this article, we report a novel deletion compound combined with a causative variant in <jats:italic>WDR35<\/jats:italic> gene leading to short-rib thoracic dysplasia 7 (SRTD7) with or without polydactyly using WES.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study involved a Chinese fetus with clinical features of skeletal dysplasia on ultrasound imaging, in whom chromosome abnormalities and copy number variants (CNVs) were detected by chromosomal microarray analysis (CMA), and sequence variants were detected by WES. The obtained results were further verified by Sanger sequencing or real time quantitative PCR (qPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No chromosomal abnormality or CNVs were identified in the fetus by CMA. However, WES result revealed a 14.38-kb large novel deletion compound covering exon 7 to exon 12 combined with a missense variant NM_001006657.2:c.932G&amp;gt;T(p.W311l) in <jats:italic>WDR35<\/jats:italic>. Both variants were thought of as pathogenic, which was further confirmed by Sanger sequencing and qPCR. In addition, two compound heterozygous variants NM_015102.5:c.[1196A&amp;gt;G(p.E399G)];[1972C&amp;gt;T(p.R658*)] in <jats:italic>NPHP4<\/jats:italic> gene were also identified in the fetus, which may be partially responsible for fetal kidney hyperechogenicity and oligohydramnios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study reporting a novel deletion compound combined with a causative missense variant in <jats:italic>WDR35<\/jats:italic> leading to SRTD7. This finding may broaden the spectrum of variants of <jats:italic>WDR35<\/jats:italic> gene and provide a valuable reference for clinical counseling of related abnormalities in pregnancies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1503455","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:11:58Z","timestamp":1736835118000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Prenatal diagnosis of novel compound heterozygous variants in WDR35 gene causing short-rib thoracic dysplasia 7 with or without polydactyly"],"prefix":"10.3389","volume":"12","author":[{"given":"Jianlong","family":"Zhuang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2019e","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunnuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ajhg.2010.08.004","article-title":"Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome","volume":"87","author":"Gilissen","year":"2010","journal-title":"Am J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"834064","DOI":"10.3389\/fped.2022.834064","article-title":"Case report: sequential liver after kidney transplantation in a patient with Sensenbrenner syndrome (cranioectodermal dysplasia)","volume":"10","author":"Ryzko","year":"2022","journal-title":"Front Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.ejmg.2017.08.019","article-title":"Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: example of a WDR35 mutation case and review of the literature","volume":"60","author":"Antony","year":"2017","journal-title":"Eur J Med Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1399-0004.2012.01880.x","article-title":"Novel WDR35 mutations in patients with cranioectodermal dysplasia (Sensenbrenner syndrome)","volume":"83","author":"Hoffer","year":"2013","journal-title":"Clin Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41436-019-0731-7","article-title":"The use of fetal exome sequencing in prenatal diagnosis: a point to consider document of the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"Monaghan","year":"2020","journal-title":"Genet Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3760\/cma.j.cn511374-20210920-00765","article-title":"Expert consensus on the application of prenatal exome sequencing for fetal structural anomalies","volume":"39","author":"Lou","year":"2022","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B7","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/S0140-6736(18)31940-8","article-title":"Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study","volume":"393","author":"Lord","year":"2019","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13073-022-01130-x","article-title":"Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1,618 fetuses","volume":"14","author":"Fu","year":"2022","journal-title":"Genome Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1186\/s12967-024-05468-1","article-title":"High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases","volume":"22","author":"Zeng","year":"2024","journal-title":"J Transl Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1002\/ajmg.a.31989","article-title":"An unclassifiable short rib-polydactyly syndrome with acromesomelic hypomineralization and campomelia in siblings","author":"Kannu","year":"2007","journal-title":"Am J Med Genet A"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4126","DOI":"10.1093\/hmg\/ddv152","article-title":"Specific variants in WDR35 cause a distinctive form of Ellis-Van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium","volume":"24","author":"Caparr\u00f3s-Mart\u00edn","year":"2015","journal-title":"Hum Mol Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13630-017-0051-y","article-title":"Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia","volume":"6","author":"Duran","year":"2017","journal-title":"Cilia"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1002\/ajmg.a.35608","article-title":"WDR35 mutation in siblings with Sensenbrenner syndrome: a ciliopathy with variable phenotype","author":"Bacino","year":"2012","journal-title":"Am J Med Genet A"},{"key":"B14","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1002\/ajmg.a.37514","article-title":"A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35","volume":"170","author":"Smith","year":"2016","journal-title":"Am J Med Genet A"},{"key":"B15","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.ajhg.2011.03.015","article-title":"Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis","volume":"88","author":"Mill","year":"2011","journal-title":"Am J Hum Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1038\/ng0816-970b","article-title":"The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery","volume":"48","author":"Toriyama","year":"2016","journal-title":"Nat Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"104578","DOI":"10.1016\/j.ejmg.2022.104578","article-title":"NPHP3 splice acceptor site variant is associated with infantile nephronophthisis and asphyxiating thoracic dystrophy; A rare combination","volume":"65","author":"Ijaz","year":"2022","journal-title":"Eur J Med Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s00380-021-01953-5","article-title":"Association of nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study","volume":"37","author":"Otaki","year":"2022","journal-title":"Heart Vessels"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1086\/344395","article-title":"A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution","volume":"71","author":"Otto","year":"2002","journal-title":"Am J Hum Genet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1038\/ki.2011.284","article-title":"Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies","volume":"80","author":"Chaki","year":"2011","journal-title":"Kidney Int"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1503455\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:12:02Z","timestamp":1736835122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1503455\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":20,"alternative-id":["10.3389\/fped.2024.1503455"],"URL":"https:\/\/doi.org\/10.3389\/fped.2024.1503455","relation":{},"ISSN":["2296-2360"],"issn-type":[{"type":"electronic","value":"2296-2360"}],"subject":[],"published":{"date-parts":[[2025,1,14]]},"article-number":"1503455"}}