{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:32:51Z","timestamp":1788492771936,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>WAC<\/jats:italic>\n                    \u2010related intellectual disability (ID) is a rare genetic condition characterized by a spectrum of neurodevelopmental disorders of varying severity, including global developmental delay (GDD), ID, and autism spectrum disorder. Here, we describe five affected individuals, age range 9\u201320\u2009years, and provide proof of pathogenicity of a novel splicing variant. All individuals presented with GDD, some degree of ID, and variable dysmorphism. Except for feeding difficulties, all patients were healthy without major congenital malformations or medical comorbidities. All individuals were heterozygous for de novo, previously unreported, loss of function variants in\n                    <jats:italic>WAC<\/jats:italic>\n                    . Three unrelated patients from different ethnic backgrounds shared the intronic variant c.381+4_381+7delAGTA, which was predicted to alter splicing and was initially classified as a variant of uncertain significance. Reverse transcription\u2010polymerase chain reaction analysis from one patient's cells confirmed aberrant splicing of the\n                    <jats:italic>WAC<\/jats:italic>\n                    transcript resulting in premature termination and a truncated protein p.(Gly92Alafs*2). These functional studies and the identification of several nonrelated individuals provide sufficient evidence to classify this variant as pathogenic. The clinical description of these five individuals and the three novel variants expand the genotypic and phenotypic spectrum of this ultrarare disease.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62648","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T04:20:14Z","timestamp":1641961214000},"page":"1396-1406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical and molecular characterization of five new individuals with\n                    <scp>\n                      <i>WAC<\/i>\n                    <\/scp>\n                    \u2010related intellectual disability: Evidence of pathogenicity for a novel splicing variant"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-4567","authenticated-orcid":false,"given":"Jose Andres","family":"Morales","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Genetics Division Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-6058","authenticated-orcid":false,"given":"Irene","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics University Hospital Vall d'Hebron  Barcelona Spain"},{"name":"Medicine Genetics Group Valle Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivon","family":"Cusc\u00f3","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics University Hospital Vall d'Hebron  Barcelona Spain"},{"name":"Medicine Genetics Group Valle Hebron Research Institute  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Nantes  Nantes France"},{"name":"Universit\u00e9 de Nantes, CNRS, INSERM, l'institut du thorax  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Nantes  Nantes France"},{"name":"Universit\u00e9 de Nantes, CNRS, INSERM, l'institut du thorax  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-7239","authenticated-orcid":false,"given":"Dena R.","family":"Matalon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Genetics Division Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Gomez\u2010Ospina","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Genetics Division Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8820966"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa175"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.12.019"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103069"},{"key":"e_1_2_11_6_1","unstructured":"GnomAD: Genome Aggregation Database. (2020).https:\/\/gnomad.broadinstitute.org\/"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP301214"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004772"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.05.022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11030344"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.282"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.12697"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36627"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.154"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0022-1"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38703"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488815"},{"key":"e_1_2_11_19_1","volume-title":"GeneReviews\u00ae","author":"Varvagiannis K.","year":"2017"},{"key":"e_1_2_11_20_1","unstructured":"Vissers L. deVries B. Varvagiannis K.&Dingemans L.(2018). Human disease genes website series: WAC. Human Disease Genes.https:\/\/humandiseasegenes.nl\/wac\/graph-and-chart\/"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.71"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2001.6684"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.01.024"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62648","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62648","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T05:25:54Z","timestamp":1692941154000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,12]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/ajmg.a.62648"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62648","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,12]]},"assertion":[{"value":"2021-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}