NOTCH2NLCのCGGリピート伸長を伴う神経内封入体病関連網膜症における遺伝子型-表現型相関

To report the genotype-phenotype correlations in neuronal intranuclear inclusion disease (NIID)-related retinopathy.

13 patients from 12 families (62-81 years) clinically diagnosed with late-onset NIID were studied. Best-corrected visual acuity (BCVA), Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinography (ERGs) were examined. The number of CGG repeats in NOTCH2NLC was determined. Genotype-phenotype correlations between the number of CGG repeats and the age at onset of ocular symptoms, disease duration, ellipsoid zone (EZ) length of photoreceptors in the peripapillary area, and ERGs amplitudes were determined.

All patients had expanded CGG repeats (100-177 repeat units) in the NOTCH2NLC, and 11 patients noticed ocular symptoms before cognitive decline and two noticed them in their 20 s. FAF decrease and EZ absence in the peripapillary area were observed in all cases. ERGs indicated rod-cone dysfunction. The number of repeats was significantly correlated with an amplitude of all components of scotopic and photopic ERGs except for the b-wave in dark-adapted (DA) 0.01 and DA 10.0 ERGs. The highest coefficient of correlation was found between the amplitudes of the d-wave, a-wave, and the b-wave in light-adapted (LA) ON-OFF ERG (ρ = -0.97, P < 0.001, ρ = -0.92, P < 0.01, ρ = -0.84, P < 0.01 respectively), the b-wave in LA 3.0 (ρ = -0.75, P < 0.01), and 30 Hz flicker (ρ = -0.71, P < 0.05).

Expanded CGG repeats in NOTCH2NLC develop ocular symptoms earlier than reported. The number of repeats can be a biomarker for the severity of retinal dysfunction in NIID-related retinopathy.