Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients
Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients
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DOI：
10.1111/cge.12853
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发表时间：
2017-03-01
影响因子：
3.5
通讯作者：
Voermans, N. C.
中科院分区：
文献类型：
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作者：
Demirdas, S.;Dulfer, E.;Voermans, N. C.
tenascin-X （TNX）缺陷型ehers - danlos综合征（EDS）与经典型EDS相似。由于遗传学家的认识有限，以及对TNXB基因分子分析的挑战，tnx缺陷型EDS可能未被诊断。因此，我们进行了一项观察性横断面研究。进行病史和体格检查。收集血清TNX检测结果，并结合下一代测序（NGS）、Sanger测序和多重连接依赖探针扩增（MLPA）进行突变分析。纳入常染色体隐性遗传，儿童期发病的11个家族17例患者。所有患者均有皮肤超伸展，无萎缩性瘢痕。17例患者中有16例出现关节活动过度。手脚畸形是常见的。11例患者（7个家庭）血清TNX水平检测均无。对所有家庭进行了基因检测；检测到12种不同的突变，其中大多数被怀疑导致无义mRNA介导的衰变。简而言之，tnx缺失型EDS患者通常具有广泛性关节过度活动，皮肤过度伸展和易瘀伤。与经典型相比，遗传模式为常染色体隐性遗传，不存在萎缩性瘢痕。TNXB在诊断环境中的分子分析是具有挑战性的。
The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non-sense mRNA mediated decay. In short, patients with the TNX-deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.