Holder-Espinasse Muriel, Martin-Coignard Dominique, Escande Fabienne, Manouvrier-Hanu Sylvie
Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.
Eur J Hum Genet. 2007 Nov;15(11):1115-20. doi: 10.1038/sj.ejhg.5201888. Epub 2007 Jul 4.
Increases in the number of allelic malformation syndromes have led to their classification according to their pathogenesis rather than their clinical specific phenotype. TP63 (also known as TP73L) mutations have been identified in several such syndromes characterized by autosomal dominant transmission and various combinations of ectodermal dysplasia, limb malformations and orofacial clefting. TP63 has not yet been implicated in early aging phenotype in humans, even though p63 activates a program of cellular senescence and p63-compromised mice display features of accelerated aging. We report on a family with four affected adult females presenting with Rapp-Hodgkin syndrome (RHS), an autosomal dominant clinical entity that associates anhidrotic ectodermal dysplasia with cleft lip and palate. Features between RHS and EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) have led to the recent identification of mutations in the TP63 gene, located on 3q27, in this condition. Our patients present typical clinical features of RHS, but also ophthalmic anomalies such as corneal dystrophy and premature menopause (around 30 years). The latter findings have never been reported in this condition, and could be secondary to a new TP63 deletion that has been identified in this family.
等位基因畸形综合征数量的增加促使人们根据其发病机制而非临床特定表型对其进行分类。在几种此类综合征中已鉴定出TP63（也称为TP73L）突变，这些综合征具有常染色体显性遗传特征，并伴有外胚层发育异常、肢体畸形和口面部裂等多种组合。尽管p63激活细胞衰老程序且p63功能受损的小鼠表现出加速衰老的特征，但TP63尚未被认为与人类的早衰表型有关。我们报告了一个有四名成年女性患病的家庭，她们患有拉普-霍奇金综合征（RHS），这是一种常染色体显性临床病症，其特征为无汗性外胚层发育异常合并唇腭裂。RHS与EEC综合征（缺指（趾）、外胚层发育异常和唇/腭裂）之间的特征相似，这导致最近在这种病症中发现了位于3q27的TP63基因突变。我们的患者表现出RHS的典型临床特征，但也有眼部异常，如角膜营养不良和过早绝经（约30岁）。后一种发现此前从未在这种病症中报道过，可能继发于在这个家庭中鉴定出的一种新的TP63缺失。
