Retinitis Pigmentosa withEYSMutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations

Abstract

The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.

Eyes shut homolog is required for maintaining the ciliary pocket and survival of photoreceptors in zebrafish

“…We have named these mutant alleles as eys sny593 , eys sny14 , eys sny13 , and eys sny10 in accordance with the convention on zebrafish mutant line designation. All of these mutations occur within exon 2 and are expected to disrupt the reading frame resulting in the loss of all EGF and laminin G domains, which is similar to the presumed pathogenic mutations L60WfsX3 (Arai et al, 2015), Q27RfsX16 (Barragán et al, 2010), T135LfsX25 (Bandah-Rozenfeld et al, 2010), and N137VfsX24 (Audo et al, 2010) found in human patients. For example, the effects on EYS proteins for eys sny593 , eys sny14 , and eys sny10 mutations are E50SfsX11, M49QfsX47, and T47RfsX5.…”

“…Mutations in EYS account for 5-16% of all autosomal recessive cases in Europe (Audo et al, 2010; Barragán et al, 2010; Littink et al, 2010b) and the most prevalent form of inherited retinal dystrophy in Japan (Arai et al, 2015; Iwanami et al, 2012). Loss of photoreceptors has been confirmed by histopathological evaluation of the patients' retina (Bonilha et al, 2015).…”

EYS Is a Protein Associated with the Ciliary Axoneme in Rods and Cones

“…Mutations in the EYS gene are the commonest cause of non-syndromic autosomal recessive retinitis pigmentosa (arRP; OMIM #602772) [3, 4]. The mutation prevalence ranges from 5% in the Dutch and Canadian populations [5] to 18–23.5% in the Japanese population [6], where mutations in EYS have emerged as the most frequent cause of inherited retinal dystrophies overall [7]. Of note, there has been a report of a Japanese individual diagnosed with cone-rod dystrophy caused by a compound heterozygous mutation in EYS [8].…”

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

“…4 EYS is an important and common cause of RP in the Japanese, Spanish, British, Chinese, Israelis, and Palestinians. [5][6][7][8][9] Furthermore, a report has described that EYS-associated RP patients share a relatively uniform phenotype with near-normal central visual function up to their 20s. 10 We have previously reported that severity of RP patients with EYS mutations was relatively moderate among RP patients with various mutations.…”