{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:49:02Z","timestamp":1791395342596,"version":"4.3.3"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,29]],"date-time":"2017-09-29T00:00:00Z","timestamp":1506643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Microcephalic primordial dwarfisms are a group of rare Mendelian disorders characterized by severe growth retardation and microcephaly. The molecular basis is heterogeneous, with disease\u2010causing genes implicated in different cellular functions. Recently, 2 patients were reported with the same homozygous variant in the <jats:italic><jats:styled-content style=\"fixed-case\">WDR4<\/jats:styled-content><\/jats:italic> gene, coding for an enzyme responsible for the <jats:styled-content style=\"fixed-case\">m<jats:sup>7<\/jats:sup>G<jats:sub>46<\/jats:sub><\/jats:styled-content> post transcriptional modification of <jats:styled-content style=\"fixed-case\">tRNA<\/jats:styled-content>. We report here 2 sisters harboring compound heterozygous variants of <jats:italic><jats:styled-content style=\"fixed-case\">WDR4<\/jats:styled-content><\/jats:italic>. Their phenotype differs from that of the first 2 described patients: they both have a severe microcephaly but only one of the 2 sisters had a head circumference at birth below \u22122 <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>, their intellectual deficiency is less severe, and they have a growth hormone deficiency and a partial hypogonadotropic hypogonadotropism. One of the 2 variants is a frameshift mutation, and the other one is a missense occurring in the same nucleotide affected by the first reported pathogenic variant, which could therefore be a mutational hot spot. The description of these 2 sisters allow us to confirm that biallelic variants in the <jats:italic><jats:styled-content style=\"fixed-case\">WDR4<\/jats:styled-content><\/jats:italic> gene can lead to a specific phenotype, characterized by severe growth retardation and microcephaly.<\/jats:p>","DOI":"10.1111\/cge.13074","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T11:35:51Z","timestamp":1497526551000},"page":"374-377","source":"Crossref","is-referenced-by-count":56,"title":["Further delineation of the phenotype caused by biallelic variants in the <i><scp>WDR4<\/scp><\/i> gene"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-5684","authenticated-orcid":false,"given":"A.","family":"Trimouille","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Lasseaux","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Barat","sequence":"additional","affiliation":[{"name":"Service d'Endocrinologie P\u00e9diatrique CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Deiller","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Drunat","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique H\u00f4pital Robert Debr\u00e9, PROTECT  Paris France"},{"name":"H\u00f4pital Robert Debr\u00e9 INSERM U1141  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Rooryck","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"INSERM U1211 \u2013 Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) Universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Arveiler","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"INSERM U1211 \u2013 Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) Universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Bordeaux  Bordeaux France"},{"name":"INSERM U1211 \u2013 Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme (MRGM) Universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320120103"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320120104"},{"key":"e_1_2_7_4_1","first-page":"39","article-title":"Malformation syndromes. A selected miscellany","volume":"11","author":"Gorlin RJ","year":"1975","journal-title":"Birth Defects Orig Artic Ser"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.169037"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0779-x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355838202024019"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.01.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0786-y"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1523"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35447"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35681"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2007.10.025"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T07:25:38Z","timestamp":1695885938000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,29]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/cge.13074"],"URL":"https:\/\/doi.org\/10.1111\/cge.13074","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,29]]}}}