Burch G H, Gong Y, Liu W, Dettman R W, Curry C J, Smith L, Miller W L, Bristow J
Department of Pediatrics, University of California-San Francisco 94143, USA.
Nat Genet. 1997 Sep;17(1):104-8. doi: 10.1038/ng0997-104.
The tenascins are a family of large extracellular matrix proteins with at least three members: tenascin-X (TNX), tenascin-C (TNC, or cytotactin) and tenascin-R (TN-R, or restrictin). Although the tenascins have been implicated in a number of important cellular processes, no function has been clearly established for any tenascin. We describe a new contiguous-gene syndrome, involving the CYP21B and TNX genes, that results in 21-hydroxylase deficiency and a connective-tissue disorder consisting of skin and joint hyperextensibility, vascular fragility and poor wound healing. The connective tissue findings are typical of the Ehlers-Danlos syndrome (EDS). The abundant expression of TNX in connective tissues is consistent with a role in EDS, and our patient's skin fibroblasts do not synthesize TNX protein in vitro or in vivo. His paternal allele carries a novel deletion arising from recombination between TNX and its partial duplicate gene, XA, which precludes TNX synthesis. Absence of TNX mRNA and protein in the proband, mapping of the TNX gene and HLA typing of this family suggest recessive inheritance of TNX deficiency and connective-tissue disease. Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential role for TNX in connective-tissue structure and function.
腱生蛋白是一类大型细胞外基质蛋白家族，至少包括三个成员：腱生蛋白-X（TNX）、腱生蛋白-C（TNC，或细胞趋化蛋白）和腱生蛋白-R（TN-R，或限制蛋白）。尽管腱生蛋白与许多重要的细胞过程有关，但尚未明确任何一种腱生蛋白的功能。我们描述了一种新的连续基因综合征，涉及CYP21B和TNX基因，该综合征导致21-羟化酶缺乏以及一种结缔组织疾病，其特征为皮肤和关节过度伸展、血管脆弱及伤口愈合不良。这些结缔组织表现是埃勒斯-当洛综合征（EDS）的典型特征。TNX在结缔组织中的大量表达与它在EDS中的作用相符，而且我们患者的皮肤成纤维细胞在体外或体内均不合成TNX蛋白。其父亲的等位基因携带一个由TNX与其部分重复基因XA之间的重组产生的新缺失，这使得TNX无法合成。先证者中TNX mRNA和蛋白的缺失、TNX基因的定位以及该家族的HLA分型提示TNX缺乏和结缔组织疾病为隐性遗传。尽管TNX在EDS发病机制中的具体作用尚不确定，但该患者的发现提示TNX在结缔组织结构和功能中具有独特且重要的作用。
