GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa-like phenotype.
GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa-like phenotype.
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重叠弹性假黄瘤/皮肤松弛样表型患者的GGCX突变
DOI：
10.1111/bjd.19576
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Li D;Ryu E;Saeidian AH;Youssefian L;Oliphant E;Terry SF;Tong PL;Uitto J;Haass NK;Li Q
弹性纤维性假黄瘤（PXE）是一种多系统疾病，以结缔组织异位矿化为特征，主要表现在皮肤、眼睛和心血管系统。经典形式的PXE是由编码主要在肝脏中表达的ABCC 6蛋白的ABCC 6基因突变引起的。拉克萨（CL）表现为皮肤松弛和下垂，失去了反冲力。在2009年，我们调查了一个19岁的患者与重叠的皮肤特征的PXE和CL，连同α地中海贫血。遗传分析未能确定ABCC 6中的致病突变。最近，我们开发了下一代测序技术的基因靶向面板。该小组有29个基因，其中22个，包括ABCC 6和GGCX，与异位矿化表型相关。突变分析鉴定了两个杂合GGCX突变，外显子2中的c.200_201delTT和外显子7中的c.763G>A，p.V255M。GGCX基因编码激活肝脏中凝血因子所必需的γ-谷氨酰羧化酶。先前报道p.V255M突变导致体外γ-谷氨酰羧化酶活性降低，而c.200_201delTT突变是新的。先前的研究报道，GGCX突变导致与或不与多种维生素K依赖性凝血因子缺乏症相关的PXE/CL皮肤表型。我们的病人有松弛多余的皮肤，中度至重度血管样条纹，真皮中层弹性结构的特征性钙化，与PXE/CL重叠一致，但没有凝血异常。我们的研究扩展了具有PXE样表型的患者中的GGCX突变景观。
Pseudoxanthoma elasticum (PXE) is a multisystem disorder characterized by ectopic mineralization of connective tissues with primary manifestations in the skin, eyes, and cardiovascular system. The classic forms of PXE are caused by mutations in the ABCC6 gene encoding the ABCC6 protein expressed primarily in the liver. Cutis laxa (CL) manifests with loose and sagging skin with loss of recoil. In 2009 we investigated a 19-year-old patient with overlapping cutaneous features of PXE and CL, together with alpha thalassemia. Genetic analysis failed to identify pathogenic mutations in ABCC6. More recently we developed a gene-targeted panel of next-generation sequencing technology. This panel has 29 genes, 22 of them, including ABCC6 and GGCX, being associated with ectopic mineralization phenotypes. Mutation analysis identified two heterozygous GGCX mutations, c.200_201delTT in exon 2 and c.763G>A, p.V255M in exon 7. The GGCX gene encodes a γ-glutamyl carboxylase necessary for activation of blood coagulation factors in the liver. The p.V255M mutation was previously reported to result in reduced γ-glutamyl carboxylase activity in vitro while the c.200_201delTT mutation is novel. Previous studies reported that mutations in GGCX cause PXE/CL skin phenotypes in association with or without multiple vitamin K-dependent coagulation factor deficiency. Our patient had loose redundant skin, moderate to severe angioid streaks, characteristic calcification of elastic structures in mid-dermis, consistent with PXE/CL overlap, but no coagulation abnormalities. Our studies expand the GGCX mutation landscape in patients with PXE-like phenotypes.
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影响因子：
6.5
作者：
Kariminejad, Ariana;Bozorgmehr, Bita;Hennekam, Raoul C.
通讯作者：
Hennekam, Raoul C.
影响因子：
6.5
作者：
Vanakker, Olivier M.;Martin, Ludovic;De Paepe, Anne
通讯作者：
De Paepe, Anne
患有假性透明瘤弹性瘤样表型的GGCX和ABCC6基因的突变。
影响因子：
6.5
作者：
Li, Qiaoli;Grange, Dorothy K.;Armstrong, Nicole L.;Whelan, Alison J.;Hurley, Maria Y.;Rishavy, Mark A.;Hallgren, Kevin W.;Berkner, Kathleen L.;Schurgers, Leon J.;Jiang, Qiujie;Uitto, Jouni
通讯作者：
Uitto, Jouni
影响因子：
14.9
作者：
Rentzsch P;Witten D;Cooper GM;Shendure J;Kircher M
通讯作者：
Kircher M
影响因子：
3.9
作者：
Boraldi, Federica;Lofaro, Francesco Demetrio;Quaglino, Daniela
通讯作者：
Quaglino, Daniela