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Kaoru Fujinami, Kazutoshi Yoshitake, Takaaki Hayashi, Kazuki Kuniyoshi, Shinji Ueno, Mineo Kondo, Kei Shinoda, Shuhei Kameya, Nobuhisa Nao-i, Hiroyuki Kondo, Yozo Miyake, Takeshi Iwata, Kazushige Tsunoda; Japan Eye Genetics Consortium: National Cohort Survey and Whole Exome Sequencing Results. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1758.
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© ARVO (1962-2015); The Authors (2016-present)
We describe the clinical and genetic characteristics of a nationwide cohort with inherited retinal/choroidal diseases (IRD) in Japanese population.
A cohort of 1430 affected and 686 unaffected subjects from 1247 Japanese families with IRD was ascertained between 2008 and 2018. The clinical diagnosis was performed with comprehensive ophthalmic examinations at 38 institutes throughout the nation. The cohort included retinitis pigmentosa (RP; 564 families), macular dystrophy or cone (-rod) dystrophy (MD/CORD; 167 families), occult macular dystrophy (OMD; 106 families), Stargardt disease (STGD; 68 families), Leber congenital amaurosis (LCA; 63 families), CORD with normal fundus (CORD-NF; 54 families), cone dysfunction syndrome (CDS, 51 families)congenital stationary night blindness (CSNB; 40 families), and others. Whole exome sequencing and molecular genetic analysis was performed in 829 affected and 427 unaffected subjects from 735 families.
Disease-causing variants were determined in 373/735 (50.7%) families, including 235 (235/373, 63.0%) with previously reported variants and 138 families (235/373, 37.0%) with novel variants. In total 629 detected variants, 459 (459/629, 73.0%) have been previously reported and 170 (170/629, 27.0%) are novel variants of previously reported genes. No definitive disease-causing variants or variants of putative new associated genes never reported were found in 362/735 (362/735, 49.3%) families. The disease-causing variants were determined in 159 of 287 (159/287, 55.4%) families with RP, 51 of 93 (51/92, 54.8%) families with MD/CORD, 32 of 75 (32/75, 42.7%) families with OMD, 19 of 43 (19/43, 44.2%) families with LCA, 14 of 45 (14/45, 31.3%) families with CORD-NF, 16 of 35 (16/35, 45.7%) families with CDS, and 16 of 23 (13/23, 56.5%) families with CSNB.
Conclusive molecular genetic diagnosis is obtained in half of this Japanese IRD cohort. Novel disease-causing variants are frequently revealed, which suggests the distinctive genetic background of Japanese population. This national survey provides an epidemiologic evidence of Japanese IRD, which promotes patients’ care and therapeutic trials in Japanese population.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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