Genotype Phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.4

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 : 36 participants from 21 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 1196 and 1201 (group B). Clinical parameters were compared between these two genotype groups, including age of symptom onset, age at examination, duration of disease, logarithm of the minimum angle of resolution visual acuity (LogMAR VA) of one randomly selected eye. The morphological features obtained with spectral-domain optical coherence tomography were also investigated.

Results : There are 20 patients in group A and 16 in group B. The median age of symptom onset/examination was 14.0/34.5 years (range, 2-73/11-73) and 43.5/53.0 years (range, 13-63/30-86) in groups A and B, respectively (P= 0.0012). The median duration was 9.0 years (range, 0-36) and 11.0 years (range, 0-36), respectively (P=0.9109). The median LogMAR VA in the right/left eye of groups A and B was 0.82/0.70 (range, -0.08-1.22/-0.08-1.1) and 0.41/0.56 (range, -0.08-1.0/-0.08-0.82), respectively (P= 0.0189). The classical photoreceptor findings showing both blurred ellipsoid zone (EZ) and absence of interdigitation zone (IZ) was identified in 17 (17/20, 85.0%) and 13 (13/16, 81.3%) patients in groups A and B; subtle/early photoreceptor changes of local IZ loss and relatively preserved EZ were found in 3 (3/20, 15.0%) and 3 (3/16, 18.8%) in groups A and B (P=0.7642). Comparison analyses revealed statistically significant differences between the genotype groups A and B in terms of symptom onset, age at examination, and LogMAR VA. There was no significant difference 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 counseling of patients regarding the visual severity.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.