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.
Highlights
Leber congenital amaurosis (LCA, Mendelian Inheritance in Man [MIM] 204000) is a form of retinitis pigmentosa (RP) that has the earliest onset and is the most severe form of the hereditary retinal dystrophies
Recent clinical trials with RPE65 replacement therapy have provided hope for LCA patients and their families. This study showed this form of gene therapy to be safe and effective in improving vision in patients Journal of Ophthalmology with RPE65-associated LCA [13,14,15,16]
Two novel potentially pathogenic mutations in GUCY2D were detected in both twins using targeted-next generation sequencing (NGS)
Summary
Leber congenital amaurosis (LCA, Mendelian Inheritance in Man [MIM] 204000) is a form of retinitis pigmentosa (RP) that has the earliest onset and is the most severe form of the hereditary retinal dystrophies. The estimated prevalence of LCA is 3 per 100,000 newborn babies, but LCA accounts for at least 5% of all inherited retinal dystrophies and approximately 20% of children attending schools for the blind [1, 2]. Leber congenital amaurosis is a genetically and clinically heterogeneous disease. Clinical features of LCA include blindness or severe visual impairment at birth or within the first month of life, nystagmus, very poor or absent ocular pursuit, Franceschetti’s oculodigital sign, and a severely reduced or absent electroretinogram (ERG). Other signs and symptoms which may or may not be present include photophobia, night blindness, hyperopia, macular/peripheral retinal abnormalities, keratoconus, and cataract [3,4,5]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have