Genotype-Phenotype Correlations in -Associated Retinal Dystrophies: A Multi-Center Cohort Study in JAPAN

Overview

Journal J Clin Med

Specialty General Medicine

Date 2021 Jun 2

PMID 34073704

Citations 12

Authors

Kei Mizobuchi

Takaaki Hayashi

Noriko Oishi

Daiki Kubota

Shuhei Kameya

Koichiro Higasa

Takuma Futami

Hiroyuki Kondo

Katsuhiro Hosono

Kentaro Kurata

Yoshihiro Hotta

Kazutoshi Yoshitake

Takeshi Iwata

Tomokazu Matsuura

Tadashi Nakano

Affiliations

Soon will be listed here.

Abstract

Background: Little is known about genotype-phenotype correlations of -associated retinal dystrophies in the Japanese population. We aimed to investigate the genetic spectrum of variants and provide a detailed description of the clinical findings in Japanese patients.

Methods: In total, 607 patients with inherited retinal diseases were examined using whole-exome/whole-genome sequencing (WES/WGS). PCR-based screening for an element insertion (c.4052_4053ins328/p.Tyr1352AlafsTer9) was performed in 18 patients with autosomal-recessive (AR)-retinitis pigmentosa (RP) or AR-cone dystrophy (COD)/cone-rod dystrophy (CORD), including seven patients with heterozygous variants identified by WES/WGS analysis, and 11 early onset AR-RP patients, in whom no pathogenic variant was identified. We clinically examined 25 patients (23 families) with pathogenic variants, including five patients (five families) with autosomal-dominant (AD)-RP, 13 patients (11 families) with AR-RP, and seven patients (seven families) with AR-COD/CORD.

Results: We identified 18 pathogenic variants, including seven novel variants. Interestingly, the element insertion was the most frequent variant (32.0%, 16/50 alleles). The clinical findings revealed that the age at onset and disease progression occurred significantly earlier and faster in AR-RP patients compared to AD-RP or AR-COD/CORD patients.

Conclusions: Our results suggest a genotype-phenotype correlation between variant types/locations and phenotypes (AD-RP, AR-RP, and AR-COD/CORD), and the element insertion was the most major variant in Japanese patients with -associated retinal dystrophies.

Citing Articles

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