Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63
Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63
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DOI：
10.1093/hmg/10.3.221
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发表时间：
2001-02-01
影响因子：
3.5
通讯作者：
van Bokhoven, H
中科院分区：
文献类型：
--
作者：
McGrath, JA;Duijf, PHG;van Bokhoven, H
Hay-Wells综合征，又称强直性睑下垂-外胚层发育不良-裂裂（AEC）综合征（OMIM 106260），是一种罕见的常染色体显性遗传病，以先天性外胚层发育不良为特征，包括脱发、头皮感染、指甲营养不良、下颌缺损、强直性睑下垂、唇裂和/或腭裂。这些临床症状是独特的，但也可以与其他外胚层发育不良综合征相重叠，例如，指外胚层发育不良-唇腭裂（EEC; OMIM 604292）、肢体-乳腺综合征（LMS; OMIM 603543）、肢-皮-爪-咽-牙综合征（ADULT; OMIM 103285）和隐性唇裂/腭-外胚层发育不良（CLPED1; OMIM 225060）。我们最近证明p63基因的杂合突变是EEC综合征的主要原因。连锁研究表明，相关的LMS和ADULT综合征也由p63基因突变引起。因此，p63基因突变似乎具有高度的多效性。我们分析了AEC综合征患者的p63，并在8个家族中发现了错义突变。所有突变都会引起无菌α基序（SAM）结构域的氨基酸取代，并预计会影响蛋白质之间的相互作用。相反，在EEC综合征中发现的绝大多数突变是dna结合域的氨基酸替换。因此，可以识别EEC和AEC综合征明显的基因型-表型相关性。
Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC; OMIM 604292), limb-mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/ palate-ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein-protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype-phenotype correlation can be recognized for EEC and AEC syndromes.