Retinitis Pigmentosa, Cutis Laxa, and Pseudoxanthoma Elasticum-Like Skin Manifestations Associated with GGCX Mutations
Retinitis Pigmentosa, Cutis Laxa, and Pseudoxanthoma Elasticum-Like Skin Manifestations Associated with GGCX Mutations
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DOI：
10.1038/jid.2014.191
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发表时间：
2014-09-01
影响因子：
6.5
通讯作者：
Hennekam, Raoul C.
中科院分区：
文献类型：
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作者：
Kariminejad, Ariana;Bozorgmehr, Bita;Hennekam, Raoul C.
据报道，弹性假黄瘤(PXE)样表型、皮肤松弛和多种维生素K依赖凝血因子缺乏症的患者存在γ-谷氨酰羧酶(GGCX)突变。我们报告了两个家系的13名成员的临床和分子结果，他们的表型一致，包括颈部和躯干的(PXE)样皮肤表现，躯干和上肢松弛的松弛皮肤，以及10名患者的视网膜电图证实的视网膜色素变性。未发现凝血功能异常。对ATP结合盒C亚家族成员6的分子研究没有发现致病突变。所有13个受影响的家庭成员都被发现是GGCX基因剪接点突变c.373+3G>；T的纯合子。所有被测试的父母都是突变的杂合子，健康的兄弟姐妹要么是杂合子，要么是野生型。我们认为，这些患者代表了一种迄今未见报道的与GGCX突变相关的表型。基因遗传被认为是GGCX突变携带者表型变异的原因。因此，目前的表型可能不仅仅由GGCX突变来解释，还可能受到其他基因的变异或表观遗传和环境因素的影响。
Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities. Molecular investigations of the ATP-binding cassette subfamily C member 6 did not yield causative mutations. All 13 affected family members were found to be homozygous for the splice-site mutation c.373 + 3G>T in the GGCX gene. All tested parents were heterozygous for the mutation, and healthy siblings were either heterozygous or had the wild type. We suggest that the present patients represent a hitherto unreported phenotype associated with GGCX mutations. Digenic inheritance has been suggested to explain the variability in phenotype in GGCX mutation carriers. Consequently, the present phenotype may not be explained only by the GGCX mutations only but may be influenced by variants in other genes or epigenetic and environmental factors.