Heterozygous mutation in the SAM domain of p63 underlies Rapp-Hodgkin ectodermal dysplasia
Heterozygous mutation in the SAM domain of p63 underlies Rapp-Hodgkin ectodermal dysplasia
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DOI：
10.1177/154405910308200606
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发表时间：
2003-06-01
影响因子：
7.6
通讯作者：
McGrath, JA
中科院分区：
文献类型：
--
作者：
Kantaputra, PN;Hamada, T;McGrath, JA
几种外胚层发育不良综合征，包括外胚层发育不良-裂裂（EEC）和强直球-外胚层发育不良-裂裂（AEC）综合征，已知是由p63基因突变引起的。我们研究了拉普-霍奇金综合征（RHS）是否也是由p63基因突变引起的。我们在一名泰国RHS患者的p63不育α基序（SAM）区域发现了一种杂合性从头种系错义突变S545P。这是在res中首次描述的遗传异常。氨基酸取代是迄今为止报道的p63中最下游的错义突变。患者手掌皮肤活检的组织学评估显示表皮上层角化过度和角化细胞脱离，并伴有大量角化细胞凋亡。总的来说，这些研究表明RES也是由p63突变引起的，并且与AEC综合征的临床相似性与固有突变的性质是平行的。
Several ectodermal dysplasia syndromes, including Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) and Ankyloblepharon-Ectodermal Dysplasia-Clefting (AEC) syndromes, are known to result from mutations in the p63 gene. We investigated whether Rapp-Hodgkin syndrome (RHS) is also caused by mutations in the p63 gene. We identified a heterozygous de novo germline missense mutation, S545P, in the sterile-alpha-motif (SAM) domain of p63, in a Thai patient affected with RHS. This is the first genetic abnormality to be described in RES. The amino acid substitution is the most downstream missense mutation in p63 reported thus far. Histological assessment of a skin biopsy from the patient's palm showed hyperkeratosis and keratinocyte cell-cell detachment in the upper layers of the epidermis, along with numerous apoptotic keratinocytes. Collectively, these investigations demonstrate that RES is also caused by mutations in p63 and that the clinical similarities to AEC syndrome are paralleled by the nature of the inherent mutation.