Novel GUCY2D Gene Mutations in Japanese Male Twins with Leber Congenital Amaurosis.
Novel GUCY2D Gene Mutations in Japanese Male Twins with Leber Congenital Amaurosis.
复制标题
DOI：
10.1155/2015/693468
复制
发表时间：
2015
影响因子：
1.9
通讯作者：
Hotta Y
中科院分区：
文献类型：
--
作者：
Hosono K;Harada Y;Kurata K;Hikoya A;Sato M;Minoshima S;Hotta Y
目的。Leber先天性黑色素病是一种遗传性和临床异质性疾病，是最早发病的视网膜色素变性，也是遗传性视网膜营养不良中最严重的一种。本研究旨在探讨一对日本男性双生子LCA的遗传和临床特征。方法：研究方法。为了确定致病突变，用靶向下一代测序(NGS)检测了74个已知引起RP或LCA的基因。使用定制设计的Agilent HaloPlex靶浓缩试剂盒和Illumina MiSeq测序仪进行靶向NGS。用Sanger测序证实了潜在的致病突变。临床分析基于眼科检查、眼底照相和视网膜电图(ERG)。结果。在两对双生子中都检测到了新的剪接突变c.2113+2_2113+3insT和新的错义突变p.L905P的复合杂合性GUCY2D突变。父亲和母亲分别为c.2113+2_2113+3insT和p.L905P杂合子。这对双胞胎的表型特征与之前报道的GUCY2D突变患者的表型特征相似。这包括儿童早期的视力丧失、眼球震颤、无法记录的视网膜电信号、畏光和远视。结论。据我们所知，这是用靶向-NGS检测到的带有GUCY2D突变的日本LCA双胞胎的遗传和临床特征的第一份报告。
Purpose. Leber congenital amaurosis (LCA), a genetically and clinically heterogeneous disease, is the earliest onset retinitis pigmentosa (RP) and is the most severe of hereditary retinal dystrophies. This study was conducted to investigate genetic and clinical features of LCA in a set of Japanese male twins with LCA. Methods. To identify causative mutations, 74 genes known to cause RP or LCA were examined by targeted-next generation sequencing (NGS). Targeted-NGS was performed using a custom designed Agilent HaloPlex target enrichment kit with Illumina Miseq sequencer. Identified potential pathogenic mutations were confirmed using Sanger sequencing. Clinical analyses were based on ophthalmic examination, fundus photography, and electroretinography (ERG). Results. Compound heterozygous GUCY2D mutations of novel splicing mutation c.2113+2_2113+3insT and novel missense mutation p.L905P were detected in both twins. Their father and mother were heterozygous for c.2113+2_2113+3insT and p.L905P, respectively. The twins had phenotypic features similar to those previously reported in patients with GUCY2D mutations. This included early childhood onset of visual loss, nystagmus, unrecordable ERG, photophobia, and hyperopia. Conclusions. To the best of our knowledge, this is the first report of genetic and clinical features of Japanese LCA twins with GUCY2D mutation, which were detected using targeted-NGS.
登录
查看更多内容
影响因子：
1.4
作者：
Marmor, M. F.;Fulton, A. B.;Bach, M.
通讯作者：
Bach, M.
影响因子：
3.7
作者：
Hosono K;Ishigami C;Takahashi M;Park DH;Hirami Y;Nakanishi H;Ueno S;Yokoi T;Hikoya A;Fujita T;Zhao Y;Nishina S;Shin JP;Kim IT;Yamamoto S;Azuma N;Terasaki H;Sato M;Kondo M;Minoshima S;Hotta Y
通讯作者：
Hotta Y
影响因子：
4.2
作者：
Mihelec, Marija;Pearson, Rachael A.;Ali, Robin R.
通讯作者：
Ali, Robin R.
影响因子：
3.9
作者：
Neveling, Kornelia;Collin, Rob W. J.;Gilissen, Christian;van Huet, Ramon A. C.;Visser, Linda;Kwint, Michael P.;Gijsen, Sabine J.;Zonneveld, Marijke N.;Wieskamp, Nienke;de Ligt, Joep;Siemiatkowska, Anna M.;Hoefsloot, Lies H.;Buckley, Michael F.;Kellner, Ulrich;Branham, Kari E.;den Hollander, Anneke I.;Hoischen, Alexander;Hoyng, Carel;Klevering, B. Jeroen;van den Born, L. Ingeborgh;Veltman, Joris A.;Cremers, Frans P. M.;Scheffer, Hans
通讯作者：
Scheffer, Hans
影响因子：
4.4
作者：
Li Y;Wang H;Peng J;Gibbs RA;Lewis RA;Lupski JR;Mardon G;Chen R
通讯作者：
Chen R