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Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.

Arai Y, Maeda A, Hirami Y, Ishigami C, Kosugi S, Mandai M, Kurimoto Y, Takahashi M - J Ophthalmol (2015)

Bottom Line: We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%.This study found 43 novel sequence variants.EYS mutations are the most prevalent among Japanese patients with IRD.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

A stepwise screening for patients with IRD. Molecular diagnosis was performed with a stepwise screening methodology. Patients with RP were initially screened with 15 genes, and additional 27 genes were sequenced when the initial screening failed to detect mutations. Disease-specific genes were sequenced for patients with other IRD.
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fig1: A stepwise screening for patients with IRD. Molecular diagnosis was performed with a stepwise screening methodology. Patients with RP were initially screened with 15 genes, and additional 27 genes were sequenced when the initial screening failed to detect mutations. Disease-specific genes were sequenced for patients with other IRD.

Mentions: Genomic DNA was extracted from peripheral lymphocytes using standard procedures. Mutation screening was performed by a stepwise direct sequencing utilizing one or two panels of genes listed in Supplemental Tables S1(A) and S1(B) in Supplementary Material available online at http://dx.doi.org/10.1155/2015/819760 for patients with RP (Figure 1). Only patients whose sequence variants were not detectable underwent additional screening with the 2nd panel. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes was conducted by analyzing the following genes for mutations (Supplemental Table S1(C)): ABCA4 and RDS/PRPH2 for Stargardt disease, CHM for choroideremia, CYP4V2 for Bietti crystalline dystrophy, SAG for Oguchi disease, VMD2 for Best disease, USH2A for Usher syndrome, RS1 for retinoschisis, RDS/PRPH2 for central areolar choroidal dystrophy, and RDH5 and RLBP1 for fundus albipunctatus. In silico analysis was performed to evaluate the potential deleterious effects of novel missense mutations utilizing the following four computational prediction algorithms: PolyPhen2 (http://genetics.bwh.harvard.edu/pph2/index.shtml), SIFT (http://sift.jcvi.org/), PMut (http://mmb2.pcb.ub.es:8080/PMut/PMut.jsp), and SNAP (https://rostlab.org/services/snap/). Variants were determined to carry potential deleterious effects when 50% and higher rates of the programs predict their pathogenicity. Segregation analysis was also applied to families with newly identified mutations.


Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.

Arai Y, Maeda A, Hirami Y, Ishigami C, Kosugi S, Mandai M, Kurimoto Y, Takahashi M - J Ophthalmol (2015)

A stepwise screening for patients with IRD. Molecular diagnosis was performed with a stepwise screening methodology. Patients with RP were initially screened with 15 genes, and additional 27 genes were sequenced when the initial screening failed to detect mutations. Disease-specific genes were sequenced for patients with other IRD.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4487330&req=5

fig1: A stepwise screening for patients with IRD. Molecular diagnosis was performed with a stepwise screening methodology. Patients with RP were initially screened with 15 genes, and additional 27 genes were sequenced when the initial screening failed to detect mutations. Disease-specific genes were sequenced for patients with other IRD.
Mentions: Genomic DNA was extracted from peripheral lymphocytes using standard procedures. Mutation screening was performed by a stepwise direct sequencing utilizing one or two panels of genes listed in Supplemental Tables S1(A) and S1(B) in Supplementary Material available online at http://dx.doi.org/10.1155/2015/819760 for patients with RP (Figure 1). Only patients whose sequence variants were not detectable underwent additional screening with the 2nd panel. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes was conducted by analyzing the following genes for mutations (Supplemental Table S1(C)): ABCA4 and RDS/PRPH2 for Stargardt disease, CHM for choroideremia, CYP4V2 for Bietti crystalline dystrophy, SAG for Oguchi disease, VMD2 for Best disease, USH2A for Usher syndrome, RS1 for retinoschisis, RDS/PRPH2 for central areolar choroidal dystrophy, and RDH5 and RLBP1 for fundus albipunctatus. In silico analysis was performed to evaluate the potential deleterious effects of novel missense mutations utilizing the following four computational prediction algorithms: PolyPhen2 (http://genetics.bwh.harvard.edu/pph2/index.shtml), SIFT (http://sift.jcvi.org/), PMut (http://mmb2.pcb.ub.es:8080/PMut/PMut.jsp), and SNAP (https://rostlab.org/services/snap/). Variants were determined to carry potential deleterious effects when 50% and higher rates of the programs predict their pathogenicity. Segregation analysis was also applied to families with newly identified mutations.

Bottom Line: We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%.This study found 43 novel sequence variants.EYS mutations are the most prevalent among Japanese patients with IRD.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus