Two Novel Mutations in the EYS Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population
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{"title"=>"Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the japanese population", "type"=>"journal", "authors"=>[{"first_name"=>"Katsuhiro", "last_name"=>"Hosono", "scopus_author_id"=>"7005810795"}, {"first_name"=>"Chie", "last_name"=>"Ishigami", "scopus_author_id"=>"25122118800"}, {"first_name"=>"Masayo", "last_name"=>"Takahashi", "scopus_author_id"=>"7406843442"}, {"first_name"=>"Dong Ho", "last_name"=>"Park", "scopus_author_id"=>"56321807400"}, {"first_name"=>"Yasuhiko", "last_name"=>"Hirami", "scopus_author_id"=>"6505922815"}, {"first_name"=>"Hiroshi", "last_name"=>"Nakanishi", "scopus_author_id"=>"55166672900"}, {"first_name"=>"Shinji", "last_name"=>"Ueno", "scopus_author_id"=>"7402327647"}, {"first_name"=>"Tadashi", "last_name"=>"Yokoi", "scopus_author_id"=>"7201620330"}, {"first_name"=>"Akiko", "last_name"=>"Hikoya", "scopus_author_id"=>"8568287400"}, {"first_name"=>"Taichi", "last_name"=>"Fujita", "scopus_author_id"=>"42561235400"}, {"first_name"=>"Yang", "last_name"=>"Zhao", "scopus_author_id"=>"55001670700"}, {"first_name"=>"Sachiko", "last_name"=>"Nishina", "scopus_author_id"=>"6701673639"}, {"first_name"=>"Jae Pil", "last_name"=>"Shin", "scopus_author_id"=>"56517350400"}, {"first_name"=>"In Taek", "last_name"=>"Kim", "scopus_author_id"=>"35268987400"}, {"first_name"=>"Shuichi", "last_name"=>"Yamamoto", "scopus_author_id"=>"35768793000"}, {"first_name"=>"Noriyuki", "last_name"=>"Azuma", "scopus_author_id"=>"7101731631"}, {"first_name"=>"Hiroko", "last_name"=>"Terasaki", "scopus_author_id"=>"7103159537"}, {"first_name"=>"Miho", "last_name"=>"Sato", "scopus_author_id"=>"7405721934"}, {"first_name"=>"Mineo", "last_name"=>"Kondo", "scopus_author_id"=>"7403405237"}, {"first_name"=>"Shinsei", "last_name"=>"Minoshima", "scopus_author_id"=>"7102383696"}, {"first_name"=>"Yoshihiro", "last_name"=>"Hotta", "scopus_author_id"=>"55773569100"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84857172787", "doi"=>"10.1371/journal.pone.0031036", "pui"=>"364281304", "pmid"=>"22363543", "scopus"=>"2-s2.0-84857172787", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"d3fcebc0-83c6-356c-b1b1-abfe986deecb", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/two-novel-mutations-eys-gene-possible-major-causes-autosomal-recessive-retinitis-pigmentosa-japanese", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>11}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "South Africa"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/681310"], "description"=>"<p>Partial sequence of the <i>EYS</i> gene showing the normal control sequences (A-1 through F-1), heterozygous mutation sequences (A-2 through F-2), and homozygous mutation sequences (A-3 and C-3). Deduced amino acids are indicated under the sequence trace. The mutation location is indicated either by an arrow (for a nucleotide change) or a horizontal line (to show 2 nucleotides between which the insertion occurred). (A) c.4957_4958insA; p.S1653KfsX2 (Exon 26), (B) c.6557G>A; p.G2186E (Exon 32), (C) c.8868C>A; p.Y2956X (Exon 44), (D) c.8351T>G; p.L2784R (Exon 44), (E) c.7793G>A; p.G2598D (Exon 40), (F) c.2522_2523insA; p.Y841X (Exon 16).</p>", "links"=>[], "tags"=>["pathogenic"], "article_id"=>351776, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electropherograms_of_the_6_likely_pathogenic_EYS_mutations_/351776", "title"=>"Electropherograms of the 6 likely pathogenic <i>EYS</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-17 00:29:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/681817"], "description"=>"<p>Nucleotide numbering reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence FM209056, according to the nomenclature recommended by the Human Genome Variation Society (<a href=\"http://www.hgvs.org/mutnomen\" target=\"_blank\">www.hgvs.org/mutnomen</a>). The initiation codon is codon 1. None of these 13 mutations were found in the Japanese controls.</p>a<p>EYS has a signal peptide, a putative coiled-coil, 29 EGF, and 5 Laminin G domains. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone-0031036-g003\" target=\"_blank\">Fig. 3</a>.</p>b<p>Segregation analysis has been performed. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone-0031036-g002\" target=\"_blank\">Fig. 2</a>.</p><p>In RP56K and RP81K, 2 pathogenic alleles were considered to be on different chromosomes (compound heterozygous). See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone-0031036-g002\" target=\"_blank\">Fig. 2</a>.</p>", "links"=>[], "tags"=>["japanese"], "article_id"=>352275, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.t001", "stats"=>{"downloads"=>7, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutation_spectrum_of_the_EYS_gene_in_Japanese_families_/352275", "title"=>"Mutation spectrum of the <i>EYS</i> gene in Japanese families.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-17 00:37:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/346873"], "description"=>"<div><p>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 <em>EYS</em> (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of <em>EYS</em> mutations in 100 Japanese arRP patients. To determine the prevalence of <em>EYS</em> mutations, all <em>EYS</em> exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in <em>EYS</em>, 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 <em>EYS</em> 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 <em>EYS</em> in the pathogenesis of arRP in the Japanese population. Mutation spectrum of <em>EYS</em> 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 <em>EYS</em> gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan.</p> </div>", "links"=>[], "tags"=>["mutations", "are", "causes", "autosomal", "recessive", "retinitis", "pigmentosa", "japanese"], "article_id"=>128565, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036", "stats"=>{"downloads"=>4, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Two_Novel_Mutations_in_the_EYS_Gene_Are_Possible_Major_Causes_of_Autosomal_Recessive_Retinitis_Pigmentosa_in_the_Japanese_Population/128565", "title"=>"Two Novel Mutations in the <em>EYS</em> Gene Are Possible Major Causes of Autosomal Recessive Retinitis Pigmentosa in the Japanese Population", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-17 02:22:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/681473"], "description"=>"<p>Below the individuals, genotypes are presented for either p.S1653KfsX2 (M1), p.L2784R (M2), p.Y2956X (M3), p.Y841X (M4), or p.G2186E (M5) detected to segregate with RP. M1/M1 represents homozygous mutation. M1/+ indicates heterozygous carriers, +/+ indicates individuals carrying 2 wild-type alleles, whereas M1/M2 represents individuals presenting both mutations as compound heterozygous. Square boxes indicate men, circles denote women, and affected individuals are pointed out by a black symbol. Slashed symbols indicate deceased individuals. The probands are indicated with an arrow. NA denotes unavailable DNA samples.</p>", "links"=>[], "tags"=>["was", "mutation"], "article_id"=>351942, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.g002", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pedigrees_of_the_families_that_was_available_for_mutation_analysis_/351942", "title"=>"Pedigrees of the families that was available for mutation analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-17 00:32:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/681940"], "description"=>"a<p>EYS contains a signal peptide, a putative coiled-coil, 29 EGF, and 5 laminin G domains. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone-0031036-g003\" target=\"_blank\">Fig. 3</a>.</p>b<p>hu/o/m/ho/d/op/p/c/z/dr denotes Human/Orangutan/Marmoset/Horse/Dog/Opossum/Platypus/Chicken/Zebrafish/Drosophila EYS orthologs, respectively. The hyphen (-) indicates that genomic sequence of corresponding region in the species was reported to be unknown <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone.0031036-Barragn1\" target=\"_blank\">[5]</a>.</p>c<p>SIFT, PolyPhen2 (only the HumDiv data are shown), PMut, and SNAP were used as reference data to evaluate the pathogenicity of the missense mutations. c.77G>A, c.2923T>C, c.7793G>A, c.8351T>G, and c.9272T>C were predicted to be pathogenic by a number of different computational prediction programs. In addition, the c.6557G>A mutation, which had been previously reported as disease causing, was classified as pathogenic by the PolyPhen2, PMut, and SNAP programs.</p>d<p>Homozygous exon 32 deletion mutation was not detected in 200 controls.</p>", "links"=>[], "tags"=>["pathogenic", "mutations", "100", "japanese", "arrp"], "article_id"=>352396, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.t002", "stats"=>{"downloads"=>7, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_very_likely_and_possible_pathogenic_mutations_identified_in_100_Japanese_arRP_patients_/352396", "title"=>"Summary of the very likely and possible pathogenic mutations identified in 100 Japanese arRP patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-17 00:39:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/681876"], "description"=>"<p>Fifty-four sequence alterations were identified in 100 patients. These alterations were predicted to be non-pathogenic for various reasons. Some have been reported as polymorphisms in previous reports. Newly identified alterations within the exons, except for c.334G>A and c.8923T>C, were also found in the control chromosome. The hyphen (-) indicates that genomic sequence of corresponding region in the species was reported to be unknown <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031036#pone.0031036-Barragn1\" target=\"_blank\">[5]</a>.</p>a<p>hu/o/m/ho/d/op/p/c/z/dr denotes Human/Orangutan/Marmoset/Horse/Dog/Opossum/Platypus/Chicken/Zebrafish/Drosophila EYS orthologs, respectively.</p>", "links"=>[], "tags"=>["non-pathogenic", "alterations"], "article_id"=>352334, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.t003", "stats"=>{"downloads"=>4, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_possible_non_pathogenic_sequence_alterations_in_the_EYS_gene_identified_in_this_study_/352334", "title"=>"Summary of the possible non-pathogenic sequence alterations in the <i>EYS</i> gene identified in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-17 00:38:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/681662"], "description"=>"<p>SMART (<a href=\"http://smart.embl-heidelberg.de/\" target=\"_blank\">http://smart.embl-heidelberg.de/</a>) and Pfam (<a href=\"http://pfam.sanger.ac.uk/\" target=\"_blank\">http://pfam.sanger.ac.uk/</a>) were used to search protein functional domains. A coiled-coil domain identified by Barragán et al. (2010) between the EGF-like domain and laminin G domain was also indicated. Novel very likely pathogenic mutations, novel possible pathogenic mutations, and a previously described mutation are shown in bold, normal, and italic type, respectively. Six out of 9 missense mutations were found in the EGF or laminin G domains. Furthermore, 7 were located in the latter half of the protein between the putative coiled-coil region and C-terminus.</p>", "links"=>[], "tags"=>["genetics and genomics", "ophthalmology", "pathology"], "article_id"=>352117, "categories"=>["Cell Biology", "Genetics", "Medicine"], "users"=>["Katsuhiro Hosono", "Chie Ishigami", "Masayo Takahashi", "Dong Ho Park", "Yasuhiko Hirami", "Hiroshi Nakanishi", "Shinji Ueno", "Tadashi Yokoi", "Akiko Hikoya", "Taichi Fujita", "Yang Zhao", "Sachiko Nishina", "Jae Pil Shin", "In Taek Kim", "Shuichi Yamamoto", "Noriyuki Azuma", "Hiroko Terasaki", "Miho Sato", "Mineo Kondo", "Shinsei Minoshima", "Yoshihiro Hotta"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031036.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_domain_structure_and_distribution_of_identified_EYS_mutations_/352117", "title"=>"Predicted domain structure and distribution of identified <i>EYS</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-17 00:35:17"}

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Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}]}
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