Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity
Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity
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DOI：
10.1038/sj.jid.5700610
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发表时间：
2007-03-01
影响因子：
6.5
通讯作者：
De Paepe, Anne
中科院分区：
文献类型：
--
作者：
Vanakker, Olivier M.;Martin, Ludovic;De Paepe, Anne
本文报道了6例弹性假黄瘤（PXE）样表型患者的数据，其特征是过度的皮肤折叠（类似于皮肤松弛）和缺乏维生素k依赖性凝血因子（II， VII， IX和X）。将这些患者的临床、超微结构和分子表现分别与典型PXE和皮肤松弛症进行比较。临床表现与PXE有明显的重叠，表现为黄色丘疹或革质斑块，表现为点状凹陷，血管样条纹和/或眼橙色点，真皮弹性纤维碎裂和钙化。PXE的重要表型差异包括更严重的皮肤松弛，向躯干和四肢扩散，皮肤褶皱厚而坚韧，而不是局限于屈曲区，视力没有下降。此外，详细的电镜分析显示，弹性纤维的变化及其矿化与经典PXE略有不同。分子分析显示，导致PXE的ABCC6基因（atp结合盒C亚家族6成员）和已知与维生素K依赖因子缺乏有关的VKORC1基因（维生素k2,3环氧化物还原酶）均未发生因果突变。然而，GGCX基因（γ -谷氨酰羧化酶）编码一种对玻璃蛋白的g-羧化很重要的酶，在分析的7名患者中有6名发生了突变。这些发现都支持这样一种假设，即这种疾病确实代表了一种独立的临床和遗传实体，其分子背景仍有待揭示。
Data on six patients with a Pseudoxanthoma Elasticum (PXE)-like phenotype, characterized by excessive skin folding (resembling cutis laxa) and a deficiency of the vitamin K-dependent clotting factors (II, VII, IX, and X) are presented. A comparison is made between the clinical, ultrastructural, and molecular findings in these patients and those seen in classic PXE and cutis laxa, respectively. Clinical overlap with PXE is obvious from the skin manifestations of yellowish papules or leathery plaques with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences with PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization were slightly different from those in classic PXE. Molecular analysis revealed neither causal mutations in the ABCC6 gene (ATP-binding cassette subfamily C member 6), which is responsible for PXE, nor in VKORC1 (vitamin K 2,3 epoxide reductase), known to be involved in vitamin K-dependent factor deficiency. However, the GGCX gene (gamma-glutamyl carboxylase), encoding an enzyme important for g-carboxylation of gla-proteins, harbored mutations in six out of seven patients analyzed. These findings all support the hypothesis that the disorder indeed represents a separate clinical and genetic entity, the molecular background of which remains to be unraveled.