East Asian Patients with Occult Macular Dystrophy Report No.4; Genotype-Phenotype Association

Abstract

Purpose : Two hot spots in the RP1L1 gene including amino acid numbers 45 and 1196-1201 have been recently identified in occult macular dystrophy (OMD). Here, we describe the differential clinical effects of these two hotspots.

Methods : 50 participants from 29 families with OMD caused by pathogenic RP1L1 variants (i.e. Miyake’s disease) were enrolled in Japan, South Korea, and China. Patients were classified into two genotype groups; patients with p.R45W variant (group A) and subjects with missense variants located between amino acid 1196 and 1201 (group B). Clinical parameters were statistically compared between these two genotype groups, including age of symptom onset, age at examination, visual acuity in the logarithm of the minimum angle of resolution unit (VA) of one randomly selected eye. The morphological features obtained with spectral-domain optical coherence tomography were also investigated.

Results : There are 31 patients in group A and 19 in group B. The median age of onset/examination was 18.8/43.4 years (range, 2-40/11-80) and 39.4/59.5 years (range, 13-70/34-92) in groups A and B, respectively (P= 0.00013). The median duration of 22.0 years (range, 6-64) and 19.0 years (range, 8-42), in groups A and B, respectively (P= 0.9799). The median VA in the right/left eye of groups A and B was 0.70/0.71 (range, -0.08-1.22/0-1.4) and 0.41/0.44 (range, -0.08-1.0/-0.08-0.82) LogMAR unit, respectively (P= 0.0032). The classical photoreceptor findings showing both blurred ellipsoid zone (EZ) and absence of interdigitation zone (IZ) was identified in 27 (27/31, 87.1%) and 15 (15/19, 78.9%) patients in groups A and B; subtle/early photoreceptor changes of local IZ loss and relatively preserved EZ were found in 3 (3/31, 9.68%) and 3 (3/19, 15.8%) in groups A and B (P=0.6583). Comparison analyses revealed statistically significant differences in terms of age of onset, age at the latest examination, and VA. There were no significant differences with regards to the duration of the disease.

Conclusions : Different clinical severity derived from the two RP1L1 hotspots were identified; the severer phenotype of early onset and poor VA was related with p.R45W compared to 1196-1201. This genotype-phenotype association can be helpful for genetic counselling of patients regarding the visual severity.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.