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首页> 外文期刊>The Journal of investigative dermatology. >Novel Types of Mutation Responsible for the Dermatosparactic Type of Ehlers-Danlos Syndrome (Type VIIC) and Common Polymorphisms in the ADAMTS2 Gene.
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Novel Types of Mutation Responsible for the Dermatosparactic Type of Ehlers-Danlos Syndrome (Type VIIC) and Common Polymorphisms in the ADAMTS2 Gene.

机译：Ehlers-Danlos综合征（VIIC型）的皮肤滑石型和ADAMTS2基因常见的多态性负责的新型突变类型。

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摘要

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population.
机译：Ehlers-Danlos综合征（EDS）型VIIC，或皮肤剥脱型，是一种隐性遗传的结缔组织疾病，其特征是除其他症状外，由于突变使ADAMTS-2失活而导致皮肤极端脆弱，ADAMTS-2是一种酶，可切除I型前胶原的氨基肽， II和III。所有先前描述的突变都会产生过早的终止密码子，从而导致mRNA水平的显着降低。在这项研究中，我们分析了五名患者的ADAMTS2 cDNA序列，这些患者显示出与典型或潜在轻度EDS型VIIC诊断相一致的临床和/或生化特征。在两名典型的EDS型VIIC患者中检测到三种不同的改变。第一例患者是纯合子的基因组缺失，导致转录本中外显子3-5在框内跳过。在第二位患者中，母亲遗传的等位基因缺少第3外显子，从而产生过早的终止密码子，而父本等位基因具有基因组缺失，导致在mRNA水平上框内跳过第14-16号外显子。尽管外显子3-5或14-16编码的蛋白质结构域以前未被认为对ADAMTS-2活性至关重要，但是氨基胶原蛋白的加工在体外和体内均受到严重损害，为这些结构域需要适当的酶提供了证据功能。其他三位表型与EDS VIIC型相似的患者仅在正常人群中经常出现沉默和功能中性变异。

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