Multicenter genetic study of retinitis pigmentosa in Japan: I. Genetic heterogeneity in typical retinitis pigmentosa

Hayakawa, Mutsuko; Fujiki, Keiko; Kanai, Atsushi; Matsumura, Miyo; Honda, Yoshio; Sakaue, Hiroshi; Tamai, Makoto; Sakuma, Tomoko; Tokoro, Takashi; Yura, T; Katayama, Nobuyuki; Matsui, M; Yuzawa, Mitsuko; Oguchi, Yoshihisa; Akeo, Kiyoshi; Adachi, Eri; Kimura, T.; Miyake, Yoichi; Horiguchi, Masayuki; Wakabayashi, K.; Ishizaka, Nobuto; Koizumi, Keigo; Uyama, M; Tagami, Nobuko; Ishibashi, Tatsuro; Honda, Tetsuya; Nakagawa, Takashi; Takeda, Masako; Choshi, K; Watanabe, Michio; Tamura, Osamu; Shimowake, Naomi; Ueno, Hideki; Yoshida, Kazuyuki; Isashiki, Yasushi; Ohba, Norio

doi:10.1016/s0021-5155(96)00018-4

Cited by 22 publications

(10 citation statements)

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“…268000), a genetically and clinically heterogeneous retinal degeneration, is the most common worldwide, 3 having a worldwide prevalence estimated to be approximately 1 in 4000 individuals. 4–14 Currently, mutations associated with RP have been identified in more than 82 genes, of which 58 have been shown to be relevant to arRP (RetNet). However, that these 82 genes are responsible only for around 60% of RP 15,16 suggests that the number of currently unidentified genes causing RP might be quite high.…”

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confidence: 99%

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families

Chen

Jiao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeThe Pakistan Punjab population has been a rich source for identifying genes causing or contributing to autosomal recessive retinal degenerations (arRD). This study was carried out to delineate the genetic architecture of arRD in the Pakistani population.MethodsThe genetic origin of arRD in a total of 144 families selected only for having consanguineous marriages and multiple members affected with arRD was examined. Of these, causative mutations had been identified in 62 families while only the locus had been identified for an additional 15. The remaining 67 families were subjected to homozygosity exclusion mapping by screening of closely flanking microsatellite markers at 180 known candidate genes/loci followed by sequencing of the candidate gene for pathogenic changes.ResultsOf these 67 families subjected to homozygosity mapping, 38 showed homozygosity for at least one of the 180 regions, and sequencing of the corresponding genes showed homozygous cosegregating mutations in 27 families. Overall, mutations were detected in approximately 61.8 % (89/144) of arRD families tested, with another 10.4% (15/144) being mapped to a locus but without a gene identified.ConclusionsThese results suggest the involvement of unmapped novel genes in the remaining 27.8% (40/144) of families. In addition, this study demonstrates that homozygosity mapping remains a powerful tool for identifying the genetic defect underlying genetically heterogeneous arRD disorders in consanguineous marriages for both research and clinical applications.

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confidence: 99%

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families

Chen

Jiao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Given the population of Japan, approximately a 100 million, the number of patients with RP can be estimated to be 12,500–25,000. The relative frequencies of RP inheritance patterns in Japanese patients were estimated as 25.2% for autosomal recessive, 16.9% for autosomal dominant, 1.6% for X-linked, and 56.3% for simplex, indicating that most Japanese RP patients represent arRP or isolated cases [17]. Autosomal recessive and simplex cases account over 80% of RP cases in Japan (approximately 10,000–20,000 people).…”

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confidence: 99%

Two Novel Mutations in the EYS Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population

et al. 2012

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Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan.

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“…The disease can be inherited via an autosomal recessive (ar), autosomal dominant (ad), or X-linked recessive mode or may occur in isolation; more than half the cases in Japan are isolated. 1 Rod dysfunction precedes cone dysfunction; this results in the typical symptoms of night blindness, which is followed by the loss of the peripheral visual field in most cases. Subsequently, the cones in the central retina may also be affected, causing loss of visual acuity in the later stages of the disease.…”

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confidence: 99%

Clinical Phenotype in Ten Unrelated Japanese Patients with Mutations in theEYSGene

Suto

Hosono

Takahashi

et al. 2013

Ophthalmic Genetics

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Multicenter genetic study of retinitis pigmentosa in Japan: I. Genetic heterogeneity in typical retinitis pigmentosa

Cited by 22 publications

References 1 publication

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families

Two Novel Mutations in the EYS Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population

Clinical Phenotype in Ten Unrelated Japanese Patients with Mutations in theEYSGene

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