Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association

Abstract

Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15-77/25-94). The median visual acuity in the right/left eye was 0.52/0.40 (range, −0.08-2.00/−0.18-1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD

ROP18-Mediated Transcriptional Reprogramming of HEK293T Cell Reveals New Roles of ROP18 in the Interplay Between Toxoplasma gondii and the Host Cell

“…Frontiers in Cellular and Infection Microbiology | www.frontiersin.org November 2020 | Volume 10 | Article 586946 , CRX (Fujinami-Yokokawa et al, 2020), CFI and CFB (Rathi et al, 2017;Shahulhameed et al, 2020), and KCNJ13 (Toms et al, 2019) have been linked to retinopathy. Additionally, SLC38A8 contributes to congenital nystagmus (Weiner et al, 2020), and RIMS1 and CABP4 are associated with dystrophy (Sisodiya et al, 2007) and synaptic disorder of cone-rod (Littink et al, 2009), respectively.…”

Clinical and genetic characteristics of 10 Japanese patients with PROM1‐associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population

“…Pathogenic variants in the same gene may present different phenotypes. For example, relatively similar phenotypes of CORD, COD, STGD, and MD share causative genes such as ABCA4, BEST1, PRPH2, RPGR, CRX, GUCY2D, RS1, POC1B, PROM1, CNGA3, CNGB3, GUCA1A, KCNV2, and RIMS1 (Ba-Abbad, Robson, MacPhee, Webster, & Michaelides, 2019;Bouzia et al, 2020;Fujinami-Yokokawa et al, 2020;Fujinami, Lois, Davidson, et al, 2013;Fujinami, Lois, Mukherjee, et al, 2013;Fujinami et al, 2015;Georgiou et al, 2020;Gill et al, 2019;Hirji et al, 2018;Hunt, Buch, & Michaelides, 2010;Kameya et al, 2019;Kominami et al, 2018;Kondo FUJINAMI ET AL. et al, 2019;Liu et al, 2020;Mawatari et al, 2019;Michaelides et al, 2010;Mizobuchi et al, 2019;Nakanishi et al, 2016;Oishi et al, 2016;Rahman et al, 2020;Sisodiya et al, 2007;Strauss et al, 2016Strauss et al, , 2018Tanna et al, 2017;Tee et al, 2016Tee et al, , 2019.…”

“…Yang et al, 2020). Moreover, different inheritances such as autosomal dominant (AD) and autosomal recessive (AR) are associated with differences in phenotypes (Bouzia et al, 2020;Fujinami-Yokokawa et al, 2020;Gill et al, 2019;Hull et al, 2014;Liu et al, 2020;Rahman et al, 2020). PROM1 (OMIM: 604365), denoted as prominin 1, encodes a prominin pentaspan transmembrane glycoprotein selectively localized at the apical surface of murine neuroepithelial cells and is also known as CD133 and AC133 (Maw et al, 2000).…”

“…For example, relatively similar phenotypes of CORD, COD, STGD, and MD share causative genes such as ABCA4 , BEST1 , PRPH2 , RPGR , CRX , GUCY2D , RS1 , POC1B , PROM1 , CNGA3 , CNGB3 , GUCA1A , KCNV2 , and RIMS1 (Ba‐Abbad, Robson, MacPhee, Webster, & Michaelides, 2019; Bouzia et al, 2020; Fujinami‐Yokokawa et al, 2020; Fujinami, Lois, Davidson, et al, 2013; Fujinami, Lois, Mukherjee, et al, 2013; Fujinami et al, 2015; Georgiou et al, 2020; Gill et al, 2019; Hirji et al, 2018; Hunt, Buch, & Michaelides, 2010; Kameya et al, 2019; Kominami et al, 2018; Kondo et al, 2019; Liu et al, 2020; Mawatari et al, 2019; Michaelides et al, 2010; Mizobuchi et al, 2019; Nakanishi et al, 2016; Oishi et al, 2016; Rahman et al, 2020; Sisodiya et al, 2007; Strauss et al, 2016, 2018; Tanna et al, 2017; Tee et al, 2016, 2019). There are genes that are associated with different phenotypes of CORD/COD/MD and RP; EYS , CRX , PRPH2, GUCY2D , and RP1L1 (Ba‐Abbad et al, 2019; Bouzia et al, 2020; Davidson et al, 2013; Fujinami‐Yokokawa et al, 2019, 2020; Fujinami et al, 2019; Hull et al, 2014; Katagiri et al, 2018; Koyanagi et al, 2019; Liu et al, 2020; Nakamura et al, 2019; Oishi et al, 2014, 2016; L. Yang et al, 2020). Moreover, different inheritances such as autosomal dominant (AD) and autosomal recessive (AR) are associated with differences in phenotypes (Bouzia et al, 2020; Fujinami‐Yokokawa et al, 2020; Gill et al, 2019; Hull et al, 2014; Liu et al, 2020; Rahman et al, 2020).…”

RP2‐associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype–phenotype association

“…Together with the clinical features (phenotype categorization) and the patterns of inheritance, disease-causing variants were determined from the detected/filtered variants in the retinal disease-associated genes (Fujinami-Yokokawa et al, 2020;Xiao Liu et al, 2020).…”