Walker L C, Overstreet M A, Willing M C, Marini J C, Cabral W A, Pals G, Bristow J, Atsawasuwan P, Yamauchi M, Yeowell Heather N
Division of Dermatology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Med Genet A. 2004 Dec 1;131(2):155-62. doi: 10.1002/ajmg.a.30302.
Skin fibroblasts from the majority of patients with the clinical diagnosis of Ehlers-Danlos syndrome type VI (EDS VI; kyphoscoliosis type), have significantly decreased lysyl hydroxylase (LH) activity due to mutations in the LH1 gene (classified as EDS VIA: OMIM no. 225400). A rare condition exists in which patients are clinically similar but have normal levels of LH activity (designated EDS VIB: OMIM no. 229200). To define the biochemical defect, we have examined cultured fibroblasts from four EDS VIB patients for changes in the levels of the mRNAs for LH1, LH2, and LH3, collagen cross-linking patterns, and the extent of lysine hydroxylation of type I collagen alpha chains. Although normal levels of LH1 mRNA were observed in all four patients, in two patients the levels of LH2 mRNA were decreased by >50%, and a similar decrease was observed in LH3 mRNA in the other two patients. A distinct pattern of collagen cross-links, indicative of decreased lysyl hydroxylation, could be identified in EDS VIA patients, but there was no clear correlation between collagen cross-link pattern and changes in the individual LH mRNAs in EDS VIB patients. Linkage to tenascin-X was excluded in these patients. This study suggests that the basis for this form of EDS VI is genetically heterogeneous, and that alternative pathways in addition to lysine hydroxylation of collagen may be affected.
大多数临床诊断为Ⅵ型埃勒斯-当洛综合征（EDS VI；脊柱后侧凸型）的患者的皮肤成纤维细胞，由于LH1基因（归类为EDS VIA：OMIM编号225400）发生突变，其赖氨酰羟化酶（LH）活性显著降低。存在一种罕见情况，即患者临床表现相似，但LH活性水平正常（称为EDS VIB：OMIM编号229200）。为了确定生化缺陷，我们检测了4例EDS VIB患者的培养成纤维细胞中LH1、LH2和LH3的mRNA水平变化、胶原交联模式以及I型胶原α链的赖氨酸羟化程度。尽管在所有4例患者中均观察到LH1 mRNA水平正常，但在2例患者中LH2 mRNA水平降低了>50%，在另外2例患者中LH3 mRNA也有类似程度的降低。在EDS VIA患者中可识别出一种独特的胶原交联模式，表明赖氨酰羟化减少，但在EDS VIB患者中，胶原交联模式与各个LH mRNA的变化之间没有明显的相关性。这些患者排除了与腱生蛋白-X的连锁关系。这项研究表明，这种形式的EDS VI的病因在遗传上是异质性的，并且除了胶原的赖氨酸羟化之外的其他途径可能也受到影响。
