Retinal structure in Leber's congenital amaurosis caused by RPGRIP1 mutations

Daisuke Miyamichi; Sachiko Nishina; Katsuhiro Hosono; Tadashi Yokoi; Kentaro Kurata; Miho Sato; Yoshihiro Hotta; Noriyuki Azuma

doi:10.1038/s41439-019-0064-8

Retinal structure in Leber's congenital amaurosis caused by RPGRIP1 mutations

Hum Genome Var. 2019 Jun 27:6:32. doi: 10.1038/s41439-019-0064-8. eCollection 2019.

Authors

Daisuke Miyamichi¹, Sachiko Nishina², Katsuhiro Hosono¹, Tadashi Yokoi², Kentaro Kurata¹, Miho Sato¹, Yoshihiro Hotta¹, Noriyuki Azuma²

Affiliations

¹ 1Department of Ophthalmology, Hamamatsu University School of Medicine, Shizuoka, Japan.
² 2Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development, Tokyo, Japan.

Abstract

This study aimed to evaluate retinal structure in the early stage of Leber's congenital amaurosis (LCA) caused by RPGRIP1 mutations. Four patients from two families were included. Case 1 was a 13-year-old girl, cases 2 and 3 were 7-year-old monozygotic twin brothers of case 1, and case 4 was a 17-year-old boy. Comprehensive ophthalmic examinations were performed, including visual acuity measurements, perimetry, electroretinography (ERG), and optical coherence tomography (OCT). To identify potential pathogenic mutations, 74 genes known to cause retinitis pigmentosa or LCA were assessed using targeted next-generation sequencing. OCT showed photoreceptor outer nuclear layer (ONL) thinning in all patients. The lamellar structure was retained in all patients, whereas the ellipsoid zone was extinguished in cases 1, 2, and 3. In case 4, the ellipsoid zone was maintained at 9 years of age but became blurred at 17 years of age. In case 1, OCT indicated slight photoreceptor ONL thinning during the period between 7 and 11 years of age. Mutation analysis revealed RPGRIP1 mutations as the cause for autosomal recessive LCA in all patients. Photoreceptor ONL on OCT is relatively well preserved in the early stage of LCA caused by RPGRIP1 mutations.

Keywords: Genetic testing; Targeted gene repair.