{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:59:09Z","timestamp":1780505949553,"version":"3.54.1"},"reference-count":6,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report two male fetuses born to a healthy unrelated couple, with agenesis of the corpus callosum identified on detailed 20\u2010week ultrasound scans and confirmed by in\u2010utero MRI. Whole\u2010genome sequencing identified a likely pathogenic missense variant in the <jats:italic>CLCN4<\/jats:italic> gene, establishing this as the causative gene in the family. Pathogenic variants in the\u00a0CLCN4\u00a0gene cause\u00a0a\u00a0neurodevelopmental disorder (also called Raynaud\u2010Claes syndrome) inherited in an X\u2010linked pattern. The disorder is characterised by developmental delay, intellectual disability, autism spectrum disorder, epilepsy, mental health conditions, and significant feeding difficulties, predominantly, but not exclusively, affecting males. This is the first report of a prenatal phenotype associated with variants in the <jats:italic>CLCN4<\/jats:italic> gene. The diagnosis of the <jats:italic>CLCN4<\/jats:italic>\u2010related neurodevelopmental disorder in this family allowed accurate genetic counseling and discussion of reproductive choices. This leaves uncertainty about the possibility of a postnatal neurodevelopmental phenotype in heterozygous females, which we discuss.<\/jats:p>","DOI":"10.1002\/pd.6404","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T13:35:16Z","timestamp":1688650516000},"page":"1247-1250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prenatal diagnosis of CLCN4\u2010related neurodevelopmental disorder in fetuses with congenital brain anomalies"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6940-3236","authenticated-orcid":false,"given":"Zena","family":"Lam","sequence":"first","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-1194","authenticated-orcid":false,"given":"Elizabeth","family":"Wall","sequence":"additional","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Ryan","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Laboratory, Central and South Genomic Laboratory Hub  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Barber","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Laboratory, Central and South Genomic Laboratory Hub  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Kilby","sequence":"additional","affiliation":[{"name":"Fetal Medicine Centre Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"},{"name":"Illumina Granta Park Great Abington  Cambridge UK"},{"name":"College of Medical and Dental Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise K.","family":"Williams","sequence":"additional","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"NHS England.National Genomic Test Directory. Testing Criteria for Rare and Inherited Disease. V4 October 2022 (Official). Accessed 19 02 2023.https:\/\/www.england.nhs.uk\/wp\u2010content\/uploads\/2018\/08\/rare\u2010and\u2010inherited\u2010disease\u2010eligibility\u2010criteria\u2010v4.pdf"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010022\u201001852\u20109"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12201"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.193"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.135"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16906"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T16:30:53Z","timestamp":1692030653000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":6,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/pd.6404"],"URL":"https:\/\/doi.org\/10.1002\/pd.6404","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,19]]},"assertion":[{"value":"2023-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}