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

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.

Whole Locus Sequencing Identifies a Prevalent Founder Deep Intronic RPGRIP1 Pathologic Variant in the French Leber Congenital Amaurosis Cohort

“…Review of the natural history of the disease and ophthalmological data in individuals carrying deep intronic RPGRIP1 pathologic variants in homozygosity or compound heterozygosity presented with nystagmus, oculo-digital signs of Franceschetti, photophobia, hyperopia and a vision function from light perception to at best 10/200. This disease presentation is consistent with previous reports [ 19 , 20 , 21 ].…”

“…These include RPGRIP1 , a pathologic variant which has been reported to cause an early-onset cone–rod dystrophy with loss of vision in teenage (CORD13, MIM608194; [ 27 ]). Individuals carrying the c.1468-128T>G in homozygous or in heterozygous state with a loss-of-function variant or the other deep intronic c.930+77A>G change, displayed a typical RPGRIP1 -associated LCA disease [ 19 , 20 , 21 ]. This observation suggests that both the c.1468-128T>G and c.930+77A>G variants have a deleterious impact on photoreceptor connecting cilium where RPGRIP1 localises.…”

Leber’s Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations

“…[75,78]. OCT images usually demonstrate a thinner ONL and disorganized EZ, especially parafoveal [78,79]. However, Miyamichi et al reported better retention of retinal structure on OCT before the age of 5 in their case series [78].…”

“…OCT images usually demonstrate a thinner ONL and disorganized EZ, especially parafoveal [78,79]. However, Miyamichi et al reported better retention of retinal structure on OCT before the age of 5 in their case series [78]. In previous reports, despite the relative foveal sparing on OCT and fundus examination, cone response was generally diminished on ERG, but rod function remained detectable in some younger cases [77,78].…”

“…Granular hyperautofluorescence corresponding to atrophic RPE is seen on fundus autofluorescence. [75,78]. OCT images usually demonstrate a thinner ONL and disorganized EZ, especially parafoveal [78,79].…”