Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes.
Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes.
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患有假性透明瘤弹性瘤样表型的GGCX和ABCC6基因的突变。
DOI：
10.1038/jid.2008.271
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发表时间：
2009-03
影响因子：
6.5
通讯作者：
Uitto, Jouni
中科院分区：
文献类型：
--
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
经典的PXE是一种由ABCC 6基因突变引起的常染色体隐性遗传疾病，其特征是结缔组织，特别是弹性纤维的异常矿化。在这里，我们报告一个家庭与PXE样皮肤功能与多种凝血因子缺乏症，一种常染色体隐性遗传疾病与GGCX突变。先证者和她的妹妹，都有严重的皮肤发现，广泛的矿化，是GGCX基因错义突变的复合杂合子，这被证明是导致γ-谷氨酰羧化酶活性降低和基质gla蛋白羧化不足。先证者的母亲和阿姨也表现出类似PXE的皮肤变化，是GGCX错义突变（p.V255M）和ABCC 6基因无效突变（p.R1141X）的杂合子携带者，表明其皮肤发现的双基因性质。因此，GGCX错义突变复合杂合或GGCX单倍不足并结合ABCC 6基因表达杂合的个体中γ-谷氨酰羧化酶活性降低导致皮肤异常矿化，从而导致PXE样表型。这些发现扩展了PXE样表型的分子基础，并提示了多种遗传因素在病理组织矿化中的作用。
A characteristic feature of classic PXE, an autosomal recessive disorder caused by mutations in the ABCC6 gene, is aberrant mineralization of connective tissues, particularly the elastic fibers. Here, we report a family with PXE-like cutaneous features in association with multiple coagulation factor deficiency, an autosomal recessive disorder associated with GGCX mutations. The proband and her sister, both with severe skin findings with extensive mineralization, were compound heterozygotes for missense mutations in the GGCX gene, which were shown to result in reduced γ-glutamyl carboxylase activity and in under-carboxylation of matrix gla protein. The proband’s mother and aunt, also manifesting with PXE-like skin changes, were heterozygous carriers of a missense mutation (p.V255M) in GGCX and a null mutation (p.R1141X) in the ABCC6 gene, suggesting digenic nature of their skin findings. Thus, reduced γ-glutamyl carboxylase activity in individuals either compound heterozygous for a missense mutation in GGCX or with haploinsufficiency in GGCX in combination with heterozygosity for ABCC6 gene expression results in aberrant mineralization of skin leading to PXE-like phenotype. These findings expand the molecular basis of PXE-like phenotypes, and suggest a role for multiple genetic factors in pathologic tissue mineralization in general.
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DOI：
10.1073/pnas.95.2.466
发表时间：
1998-01-20
影响因子：
11.1
作者：
Berkner, KL;Pudota, BN
通讯作者：
Pudota, BN
影响因子：
20.3
作者：
Darghouth, Dhouha;Hallgren, Kevin W.;Rosa, Jean-Philippe
通讯作者：
Rosa, Jean-Philippe
影响因子：
5.5
作者：
Davies, C. A.;Jeziorska, M.;Herrick, A. L.
通讯作者：
Herrick, A. L.
影响因子：
4
作者：
Nozu, K.;Inagaki, T.;Matsuo, M.
通讯作者：
Matsuo, M.
影响因子：
4
作者：
Jin, Z-B;Mandai, M.;Kosugi, S.
通讯作者：
Kosugi, S.