Katagiri Satoshi, Negishi Yuya, Mizobuchi Kei, Urashima Mitsuyoshi, Nakano Tadashi, Hayashi Takaaki
Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
Division of Molecular Epidemiology, The Jikei University School of Medicine, Tokyo, Japan.
J Ophthalmol. 2017;2017:1079687. doi: 10.1155/2017/1079687. Epub 2017 Aug 20.
To report the spectrum of variants in Japanese patients with angioid streaks (AS).
This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the gene (exons 1 to 31) was performed using PCR-based Sanger sequencing.
Eight variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination.
We identified disease-causing variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that variants play a significant role in patients with AS in the Japanese population.
报告日本血管样条纹（AS）患者的变异谱。
这是一项单中心队列研究。对来自18个不相关日本家庭的20例AS患者的病历进行回顾性分析。采用基于聚合酶链反应（PCR）的桑格测序法对该基因（外显子1至31）进行筛查。
鉴定出8个变异作为候选致病变异。这8个变异包括5个已知变异（p.Q378X、p.R419Q、p.V848CfsX83、p.R1114C和p.R1357W）、1个先前报道的意义不明的变异（p.N428S）以及2个新变异（c.1939C>T [p.H647Y]和c.3374C>T [p.S1125F]）；后三个变异被确定为有意义的变异。以下4个变异被频繁鉴定：p.V848CfsX83（14/40个等位基因，35.0%）、p.Q378X（7/40个等位基因，17.5%）、p.R1357W（6/40个等位基因，15.0%）和p.R419Q（4/40个等位基因，10.0%）。在纳入研究的18名先证者中，有13名的变异以复合杂合或纯合状态被鉴定出来。两个家族呈现假显性遗传模式。在接受皮肤科检查的17名患者中，有15名（88.2%）出现了弹性假黄瘤。
我们在18个家族中的13个（72.2%）鉴定出处于纯合或复合杂合状态的致病变异。我们的结果表明，这些变异在日本人群的AS患者中起重要作用。
