Rinne Tuula, Spadoni Emanuela, Kjaer Klaus W, Danesino Cesare, Larizza Daniela, Kock Marianne, Huoponen Kirsi, Savontaus Marja-Liisa, Aaltonen Markku, Duijf Pascal, Brunner Han G, Penttinen Maila, van Bokhoven Hans
1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Hum Genet. 2006 Aug;14(8):904-10. doi: 10.1038/sj.ejhg.5201640. Epub 2006 May 17.
The ADULT syndrome (Acro-Dermato-Ungual-Lacrimal-Tooth, OMIM 103285) is a rare ectodermal dysplasia associated with limb malformations and caused by heterozygous mutations in p63. ADULT syndrome has clinical overlap with other p63 mutation syndromes, such as EEC (OMIM 604292), LMS (OMIM 603543), AEC (106260), RHS (129400) and SHFM4 (605289). ADULT syndrome characteristics are ectrodactyly, ectodermal dysplasia, mammary gland hypoplasia and normal lip and palate. The latter findings allow differentiation from EEC syndrome. LMS differs by milder ectodermal involvement. Here, we report three new unrelated ADULT syndrome families, all with mutations of arginine 298. On basis of 16 patients in five families with R298 mutation, we delineate the ADULT syndrome phenotype. In addition, we have documented a gain-of-function effect on the dNp63gamma isoform caused by this mutation. We discuss the possible relevance of oral squamous cell carcinoma in one patient, who carries this p63 germline mutation.
成人综合征（肢端-皮肤-指甲-泪腺-牙齿综合征，OMIM 103285）是一种罕见的外胚层发育不良，与肢体畸形相关，由p63基因的杂合突变引起。成人综合征与其他p63突变综合征存在临床重叠，如EEC综合征（OMIM 604292）、LMS综合征（OMIM 603543）、AEC综合征（106260）、RHS综合征（129400）和SHFM4综合征（605289）。成人综合征的特征包括缺指（趾）畸形、外胚层发育不良、乳腺发育不全以及唇和腭正常。后一项发现有助于与EEC综合征相鉴别。LMS综合征的不同之处在于外胚层受累较轻。在此，我们报告了三个新的非相关成人综合征家族，均存在精氨酸298突变。基于五个携带R298突变家族的16例患者，我们描述了成人综合征的表型。此外，我们记录了该突变对dNp63γ亚型产生的功能获得效应。我们讨论了一名携带这种p63种系突变的患者发生口腔鳞状细胞癌的可能相关性。
