Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks
Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks
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DOI：
10.1016/j.bbrc.2009.01.117
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发表时间：
2009-03-13
影响因子：
3.1
通讯作者：
Yuzawa, Mitsuko
中科院分区：
文献类型：
--
作者：
Sato, Naoyuki;Nakayama, Tomohiro;Yuzawa, Mitsuko
血管样条纹（AS）是由布鲁赫膜破裂引起的眼部异常。这种情况通常与弹性假黄瘤（PXE）有关。ATP结合盒亚家族C（CFTR/MRP）成员6（ABCC 6）被报道是PXE的致病基因，尽管还没有关于ABCC 6基因是否是AS的致病基因的报道。本研究的目的是使用基于单倍型的病例对照研究来分离AS的因果突变。我们对54名日本AS患者和150名对照进行了5个单核苷酸多态性（SNP）的基因分型。使用每个SNP进行简单关联研究和基于单倍型的病例对照研究。选择12例具有AS特殊单倍型的患者，然后进行基因测序。成功鉴定了6种AS致病突变（p.R419Q、p.E422K、c.2542delG、Del_Exon23、c.3774- 3775 insC和p.E1427K），其中4种为新突变。该方法既可用于鉴定多因素疾病的易感性变体，也可用于分离单基因疾病的突变。(C)2009 Elsevier Inc. All rights reserved.
Angioid streaks (AS) are eye abnormalities caused by breaks in Bruch's membrane. The condition is often associated with pseudoxanthoma elasticum (PXE). The ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6) is reported to be the causal gene for PXE, although there have been no reports on whether the ABCC6 gene is the causal gene for AS. The aims of this study are to isolate the Causal mutations for AS using a haplotype-based case-control study. We genotyped 54 Japanese AS patients and 150 controls for 5 single-nucleotide polymorphisms (SNPs). A simple association study using each SNP and a haplotype-based case-control Study were performed. Twelve patients with special haplotypes for AS were selected, and were then subjected to gene sequencing. Six variants were Successfully identified as causal mutations for AS (p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC and p.E1427K), and 4 of these were novel. This method can be applied to both identifying susceptibility variants of multifactorial diseases and isolating mutations in single-gene diseases. (C) 2009 Elsevier Inc. All rights reserved.