A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.
A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.
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DOI：
10.1056/nejmoa002939
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发表时间：
2001-10-18
影响因子：
158.5
通讯作者：
Bristow, J
中科院分区：
文献类型：
--
作者：
Schalkwijk, J;Zweers, MC;Bristow, J
背景：Ehler-Danlos综合征是一种由纤维-胶原代谢缺陷引起的遗传性结缔组织疾病。在典型的Ehler-Danlos综合征病例中，V型胶原基因突变占50%，但许多其他病例无法解释。我们调查了在结缔组织中高表达的Tenascins(细胞外基质蛋白)的缺失是否与Ehler-Danlos综合征有关。方法：采用酶联免疫吸附试验对151例Ehler-Danlos综合征的经典型、高流动性或血管型患者、75例银屑病患者、93例类风湿关节炎患者和21名健康人的血清样本进行Tenascin-X和Tenascin-C的筛查。结果：所有正常人、银屑病患者、类风湿关节炎患者和Ehler-Danlos综合征患者的血清中均有Tenascin-X的表达。其余5名无血缘关系的Ehler-Danlos综合征患者血清中未检测到Tenascin-X。通过皮肤成纤维细胞分析和皮肤免疫染色，证实这些患者存在Tenascin-X缺乏症。Tenascin-C和V型胶原在这些患者中的表达正常。所有五名患者都有关节过度活动，皮肤高度弹性，容易瘀伤，没有萎缩性疤痕。所有tenascin-X缺陷者均发现tenascin-X突变，其中1例为tenascin-X基因纯合性缺失，1例为杂合性缺失，3例为纯合性截断点突变，证实了tenascin-X的致病作用和隐性遗传模式。这一发现表明，除了胶原蛋白或胶原加工酶之外，其他因素也可能导致该综合征，并表明Tenascin-X在维持胶原基质的完整性方面发挥了核心作用。(英国医学杂志2001；345：1167-75。)版权所有(C)2001年马萨诸塞州医学会。
Background: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome.Methods: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene.Results: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the five remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance.Conclusions: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix. (N Engl J Med 2001;345:1167-75.) Copyright (C) 2001 Massachusetts Medical Society.