Molecular study of WISP3 in nine families originating from the Middle-East and presenting with progressive pseudorheumatoid dysplasia:: Identification of two novel mutations, and description of a founder effect
Molecular study of WISP3 in nine families originating from the Middle-East and presenting with progressive pseudorheumatoid dysplasia:: Identification of two novel mutations, and description of a founder effect
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DOI：
10.1002/ajmg.a.30906
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发表时间：
2005-10-01
影响因子：
2
通讯作者：
Mégarbané, A
中科院分区：
文献类型：
--
作者：
Delague, V;Chouery, E;Mégarbané, A
进行性假类风湿性发育不良 (PPD) 是一种罕见的常染色体隐性遗传综合征，其特征是存在与多个关节疼痛、僵硬和肿胀、骨质疏松症相关的脊椎骨骺发育不良，并且没有破坏性骨变化。该疾病是由位于染色体 6q22 上的 WISP3 基因突变引起的。我们在此报告对来自中东的 9 个不相关的近亲家庭进行的 WISP3 基因的分子研究：3 个来自黎巴嫩，5 个来自叙利亚，1 个来自巴勒斯坦贝都因人后裔，所有这些家庭都患有 PPD。在 WISP3 基因中鉴定出五种不同的序列变异，其中两种是新突变：密码子 197 处的 c.589G -> C 颠换，导致剪接缺陷（A197fsX201）；和 c.536_537delGT 缺失 (C179fsX)，均位于外显子 3 中。在所有其他家族中，受影响的患者对于先前描述的无义突变是纯合的，即 c.156C -> A (C52X)。有趣的是，在后面的家族中，C52X 突变总是与一种新的 c.248G -> A (G83E) 变异相关，这表明存在创始人效应。 (c) 2005 年威利-利斯。
Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive syndrome characterized by the presence of spondyloepiphyseal dysplasia associated with pain, stiffness, and swelling of multiple joints, osteoporosis, and the absence of destructive bone changes. The disorder is caused by mutations of the WISP3 gene located on chromosome 6q22. We hereby report the molecular study of the WISP3 gene in nine unrelated consanguineous families originating from the Middle-East: three from Lebanon, five from Syria, and one from Palestinian Bedouin descent, all affected with PPD. Five different sequence variations were identified in the WISP3 gene, two of them being new mutations: the c.589G -> C transversion at codon 197, responsible for a splicing defect (A197fsX201); and the c.536_537delGT deletion (C179fsX), both in exon 3. In all other families, the affected patients were homozygous for a previously described nonsense mutation, namely c.156C -> A (C52X). Interestingly, in the latter families, the C52X mutation was always found associated with a novel c.248G -> A (G83E) variation, suggesting the existence of a founder effect. (c) 2005 Wiley-Liss.