The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, M.; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

doi:10.1038/jhg.2014.65

Cited by 19 publications

(12 citation statements)

References 32 publications

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“…The detection rate of this current study would drop to 20.6% if EYS was excluded from our current analysis. As compared to recently published Japanese cohort studies [ 13 , 14 ], this study displayed a lower detection rate of USH2A . This is probably due to our two-panel screening methodology.…”

Section: Resultscontrasting

confidence: 62%

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

Arai

Maeda

Hirami

et al. 2015

Journal of Ophthalmology

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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.

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Section: Resultscontrasting

confidence: 62%

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

Arai

Maeda

Hirami

et al. 2015

Journal of Ophthalmology

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“…Because this protein belongs to cilial proteins, USH2A -associated diseases are categorized to ciliopathies [ 17 , 18 ]. In previous studies, USH2A is a frequent causal gene in Japanese RP patients as well as Caucasian RP patients, yet the mutation spectrum is different among different ethnic groups [ 19 , 20 ]. Genotype–phenotype correlation in USH2A has been reported where truncating variants are associated with more severe visual and hearing impairments [ 9 , 21 , 22 ], and similar trends have also been reported in Asians [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients

Inaba

Maeda

Yoshida

et al. 2020

IJMS

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USH2A is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in USH2A can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype–phenotype correlation in USH2A-associated RP (USH2A-RP) has been reported. Genetic and clinical characterization of USH2A-RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of USH2A were identified in 36 of 525 (6.9%) patients and genetic features of USH2A-RP were characterized. Among 36 patients with USH2A-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to USH2A alterations were similarly located throughout entire regions of the USH2A protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic USH2A-RP.

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“…The following 5 computational algorithms were used to evaluate missense mutation pathogenicity: SIFT ( http://sift.jcvi.org/www/SIFT_seq_submit2.html ), PolyPhen2 ( http://genetics.bwh.harvard.edu/pph2/ ), PMut ( http://mmb.pcb.ub.es/PMut/ ), SNAP ( http://rostlab.org/services/snap/ ), and Align-GVGD ( http://agvgd.iarc.fr/agvgd_input.php ) [ 28 ]. The secondary structure of RetGC-1, the protein encoded by GUCY2D , was predicted using PSIPRED (v3.3) on the PSIPRED server ( http://bioinf.cs.ucl.ac.uk/psipred/ ).…”

Section: Methodsmentioning

confidence: 99%

NovelGUCY2DGene Mutations in Japanese Male Twins with Leber Congenital Amaurosis

Hosono

Harada

Kurata

et al. 2015

Journal of Ophthalmology

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Purpose. Leber congenital amaurosis (LCA), a genetically and clinically heterogeneous disease, is the earliest onset retinitis pigmentosa (RP) and is the most severe of hereditary retinal dystrophies. This study was conducted to investigate genetic and clinical features of LCA in a set of Japanese male twins with LCA. Methods. To identify causative mutations, 74 genes known to cause RP or LCA were examined by targeted-next generation sequencing (NGS). Targeted-NGS was performed using a custom designed Agilent HaloPlex target enrichment kit with Illumina Miseq sequencer. Identified potential pathogenic mutations were confirmed using Sanger sequencing. Clinical analyses were based on ophthalmic examination, fundus photography, and electroretinography (ERG). Results. Compound heterozygous GUCY2D mutations of novel splicing mutation c.2113+2_2113+3insT and novel missense mutation p.L905P were detected in both twins. Their father and mother were heterozygous for c.2113+2_2113+3insT and p.L905P, respectively. The twins had phenotypic features similar to those previously reported in patients with GUCY2D mutations. This included early childhood onset of visual loss, nystagmus, unrecordable ERG, photophobia, and hyperopia. Conclusions. To the best of our knowledge, this is the first report of genetic and clinical features of Japanese LCA twins with GUCY2D mutation, which were detected using targeted-NGS.

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The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients

Cited by 19 publications

References 32 publications

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

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

Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A-Associated Retinitis Pigmentosa in Japanese Patients

NovelGUCY2DGene Mutations in Japanese Male Twins with Leber Congenital Amaurosis

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