Characterization of GUCA1A-associated Dominant Cone/cone-rod Dystrophy: Low Prevalence Among Japanese Patients with Inherited Retinal Dystrophies

Overview

Journal Sci Rep

Specialty Science

Date 2019 Nov 16

PMID 31728034

Authors

Kei Mizobuchi

Takaaki Hayashi

Satoshi Katagiri

Kazutoshi Yoshitake

Kaoru Fujinami

Lizhu Yang

Kazuki Kuniyoshi

Kei Shinoda

Shigeki Machida

Mineo Kondo

Shinji Ueno

Hiroko Terasaki

Tomokazu Matsuura

Kazushige Tsunoda

Takeshi Iwata

Tadashi Nakano

Affiliations

Soon will be listed here.

Abstract

GUCA1A gene variants are associated with autosomal dominant (AD) cone dystrophy (COD) and cone-rod dystrophy (CORD). GUCA1A-associated AD-COD/CORD has never been reported in the Japanese population. The purpose of this study was to investigate clinical and genetic features of GUCA1A-associated AD-COD/CORD from a large Japanese cohort. We identified 8 variants [c.C50_80del (p.E17VfsX22), c.T124A (p.F42I), c.C204G (p.D68E), c.C238A (p.L80I), c.T295A (p.Y99N), c.A296C (p.Y99S), c.C451T (p.L151F), and c.A551G (p.Q184R)] in 14 families from our whole exome sequencing database composed of 1385 patients with inherited retinal diseases (IRDs) from 1192 families. Three variants (p.Y99N, p.Y99S, and p.L151F), which are located on/around EF-hand domains 3 and 4, were confirmed as "pathogenic", whereas the other five variants, which did not co-segregate with IRDs, were considered "non-pathogenic". Ophthalmic findings of 9 patients from 3 families with the pathogenic variants showed central visual impairment from early to middle-age onset and progressive macular atrophy. Electroretinography revealed severely decreased or non-recordable cone responses, whereas rod responses were highly variable, ranging from nearly normal to non-recordable. Our results indicate that the three pathogenic variants, two of which were novel, underlie AD-COD/CORD with progressive retinal atrophy, and the prevalence (0.25%, 3/1192 families) of GUCA1A-associated IRDs may be low among Japanese patients.

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