title: Novel GUCY2D Gene Mutations in Japanese Male Twins with Leber Congenital Amaurosis.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hosono
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kurata
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hikoya
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Photomedical Genomics, Basic Medical Photonics Laboratory, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Shinsei
authors.initials: S
authors.lastname: Minoshima
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka 431-3192, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hotta