{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:00:18Z","timestamp":1791140418435,"version":"4.1.0"},"reference-count":44,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2002,8]]},"abstract":"<jats:p>EEC syndrome is an autosomal dominant disorder with the cardinal signs of ectrodactyly, ectodermal dysplasia, and orofacial clefts. EEC syndrome has been linked to chromosome 3q27 and heterozygous <jats:italic>p63<\/jats:italic> mutations were detected in unrelated EEC families. In addition, homozygous <jats:italic>p63<\/jats:italic> null mice exhibit craniofacial abnormalities, limb truncations, and absence of epidermal appendages, such as hair follicles and tooth primordia. In this study, we screened 39 syndromic patients, including four with EEC syndrome, five with syndromes closely related to EEC syndrome, and 30 with other syndromic orofacial clefts and\/or limb anomalies. We identified heterozygous <jats:italic>p63<\/jats:italic> mutations in three unrelated cases of EEC syndrome, two Iowa white families and one sporadic case in a Filipino boy. One family is atypical for EEC and has features consistent with Hay-Wells syndrome. In this family, the mutation ablates a splice acceptor site and, in the other two, mutations produce amino acid substitutions, R280C and R304Q, which alter conserved DNA binding sites. Germline mosaicism was detected in the founder of the mutation in one case. These three cases show significant interfamilial and intrafamilial variability in expressivity. We also screened <jats:italic>p63<\/jats:italic> in 62 patients with non-syndromic orofacial clefts, identifying an intronic single nucleotide polymorphism but finding no evidence of mutations that would explain even a subset of non-syndromic orofacial clefts. This study supports a common role for <jats:italic>p63<\/jats:italic> in classical EEC syndrome, both familial and sporadic, but not in other related or non-syndromic forms of orofacial clefts.<\/jats:p>","DOI":"10.1136\/jmg.39.8.559","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T15:54:10Z","timestamp":1033487650000},"page":"559-566","source":"Crossref","is-referenced-by-count":87,"title":["Analysis of the <i>p63<\/i> gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts"],"prefix":"10.1136","volume":"39","author":[{"given":"L L","family":"Barrow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"van Bokhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Daack-Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E C","family":"van Beersum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Gorlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2002,8,1]]},"reference":[{"key":"2025101721380312000_39.8.559.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1853"},{"key":"2025101721380312000_39.8.559.2","first-page":"16","volume":"25","year":"1988","journal-title":"Cleft Palate J"},{"key":"2025101721380312000_39.8.559.3","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569(1996)033<0406:GONOCR>2.3.CO;2"},{"key":"2025101721380312000_39.8.559.4","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0496"},{"key":"2025101721380312000_39.8.559.5","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1370"},{"key":"2025101721380312000_39.8.559.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng730"},{"key":"2025101721380312000_39.8.559.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81646-3"},{"key":"2025101721380312000_39.8.559.8","doi-asserted-by":"publisher","DOI":"10.1086\/302972"},{"key":"2025101721380312000_39.8.559.9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.3.221"},{"key":"2025101721380312000_39.8.559.10","unstructured":"Jones KL. 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