接合型大疱性表皮松解症在两个黎巴嫩家系中发现一个新的突变(法国)

作     者：Ayoub N Tomb R Charlesworth A Meneguzzi G 刘安 

作者机构：Service de Dermatologie CHU H.otel-Dieu de France BP 16-6830 Achrafieh Beyrouth Lebanon 

出 版 物：《世界核心医学期刊文摘（皮肤病学分册）》 (Digest of the World Core Medical JOurnals:Dermatology)

年 卷 期：2005年第1卷第10期

页      面：18-19页

学科分类：1002[医学-临床医学] 100206[医学-皮肤病与性病学] 10[医学] 

主　　题：层连素 遗传性皮肤病 合型 大疱性皮肤病 免疫反应性 基因分析 超微结构 胶原质 近亲结婚 皮肤标本 

摘      要：Background. Junctional epidermolysis bullosa (JEB) represents a genetically heterozygous group of bullous disorders characterized by dermo-epidermal separation resulting from mutations affecting the main dermo-epidermal adhesion factor, laminin-5,itscellularreceptor,integrin α6β4,orcollagenXVII. We report the identification of a new mutation of LAMA3, encoding laminin-5 α3 subunit in two unrelated Lebanese families. Patients and methods. Two female newborn, descending from 1st degree consanguineous marriages, presented a lethal form of EBJ-Herlitz. Histologic, ultrastructural and immunofluorescence studies were performed in order to ascertain the diagnosis and to direct genetic analysis. Mutation search was conducted through direct DNA sequencing of patients and ascendants. Results. Immunohistology of frozen skin samples revealed an extremely reduced immunoreactivity for the α3 laminin-5 subunit. The two patients were homozygous carriers (parents heterozygous) of a new missense mutation of LAMA3 gene (exon 32:4300 insA) encoding the α3 subunit of laminin-5. Resulting messenger RNA, rapidly degraded, induced an extremely reduced synthesis of α3-polypeptide, truncated in its C-terminal domain. Discussion. LAMB3 gene recurrent mutations R636X and R42X account for about 50p. 100 of EBJ cases affecting Caucasians while mutation Q1083X, affecting the same gene, is recurrent in Arab populations. The newly identified mutation results in extremely reduced synthesis of α3 chain and truncation of its C-terminal domain, which is crucial for the intermolecular interacttions of laminin-5. Our data are in accordance with recent reports suggesting geographical specificity of EBJ mutations linked to founder effects which are amplified by consanguineous marriages in genetically isolated populations. Otherwise, the observation of other unexplored cases of bullous dermatoses with early demise originating from the same region of the two families herein reported highlights the need for t