Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake’s disease); EAOMD Report No.1

Abstract

Purpose : East Asia Inherited Retinal Disease Consortium (EAIRDc) was established in 2016 to understand the etiology of East Asian patients assumed to have similar genetic background. Here, we describe the clinical and genetic characteristics of East Asian patients with occult macular dystrophy (OMD).

Methods : 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e. Miyake’s disease) were enrolled from 3 centers (11 families from Japan, 6 from South Korea and 4 from China). A detailed history was obtained and comprehensive ophthalmological examinations including spectral-domain optic coherence tomography (OCT) were performed. All detected variants in the RP1L1 gene were reviewed and in silico analysis was performed including variant effect prediction.

Results : There were 12 female and 24 male patients. The median age of symptom onset was 25.5 years (range, 2-77) and the median age at the latest examination was 46.0 years (range, 13-89). The median logarithm of the minimum angle of resolution visual acuity (LogMAR VA) in the right and left eyes was 0.60 (range, -0.08-1.22, Snellen equivalent of 20/80) and 0.60 (-0.08-1.10), respectively. The classical morphological phenotype on OCT showing both blurred ellipsoid zone (EZ) and absence of interdigitation zone (IZ) of the photoreceptors was demonstrated in 30 patients (30/36, 83.3%), subtle/early photoreceptor morphological changes of local IZ loss and relatively preserved EZ in 6 (6/36, 16.7%). Eight pathogenic RP1L1 variants were identified including seven reported and one novel variant; p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent; p.R45W (11 families, 52.3%; 1st hot spot) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 9 families (42.8%) were located in the previously reported unique motif including 6 amino acids (1196-1201; 2nd hot spot).

Conclusions : There is a large spectrum of clinical findings in OMD (Miyake’s disease), including disease onset and VA; while the characteristic photoreceptor microstructural abnormalities were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population.

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