Novel GUCY2D Gene Mutations in Japanese Male Twins with Leber Congenital Amaurosis

作者：Hosono Katsuhiro; Harada Yuko; Kurata Kentaro; Hikoya Akiko; Sato Miho; Minoshima Shinsei; Hotta Yoshihiro

来源：Journal of Ophthalmology, 2015, 2015: 693468.

DOI：10.1155/2015/693468

<jats:p><jats:italic>Purpose</jats:italic>. 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.<jats:italic>Methods</jats:italic>. 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).<jats:italic>Results</jats:italic>. Compound heterozygous<jats:italic>GUCY2D</jats:italic>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<jats:italic>GUCY2D</jats:italic>mutations. This included early childhood onset of visual loss, nystagmus, unrecordable ERG, photophobia, and hyperopia.<jats:italic>Conclusions</jats:italic>. To the best of our knowledge, this is the first report of genetic and clinical features of Japanese LCA twins with<jats:italic>GUCY2D</jats:italic>mutation, which were detected using targeted-NGS.</jats:p>

• 出版日期2015