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Next-generation sequencing-based comprehensive molecular analysis of 43 Japanese patients with cone and cone-rod dystrophies.

Oishi M, Oishi A, Gotoh N, Ogino K, Higasa K, Iida K, Makiyama Y, Morooka S, Matsuda F, Yoshimura N - Mol. Vis. (2016)

Bottom Line: Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia.Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD.The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

ABSTRACT

Purpose: To investigate the efficacy of targeted exome sequencing for mutational screening of Japanese patients with cone dystrophy (CD) or cone-rod dystrophy (CRD).

Methods: DNA samples from 43 Japanese patients with CD or CRD were sequenced using an exome-sequencing panel targeting all 193 known inherited eye disease genes and next-generation sequencing methodologies. Subsequently, candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed using distinct filtering approaches, which included the frequency of the variants in normal populations, in silico prediction tools, and cosegregation.

Results: Causative mutations were detected in 12 patients with CD or CRD (27.9%). In total, 14 distinct mutations were identified in the genes ABCA4, CDHR1, CRB1, CRX, GUCY2D, KCNV2, PROM1, PRPH2, and RDH5, including four novel mutations, c.3050+1G>A in ABCA4, c.386A>G in CDHR1, c.652+1_652+4del in CRB1, and c.454G>A in KCNV2. Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia.

Conclusions: Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD. The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

No MeSH data available.


Related in: MedlinePlus

Pedigrees of the 12 patients with cone or cone-rod dystrophy carrying pathogenic mutations. The patients’ IDs and the corresponding genes are shown above the pedigrees; +: wild-type allele.
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f1: Pedigrees of the 12 patients with cone or cone-rod dystrophy carrying pathogenic mutations. The patients’ IDs and the corresponding genes are shown above the pedigrees; +: wild-type allele.

Mentions: Pathogenic mutations were identified in 12 of the 43 patients (27.9%). A total of 14 distinct mutations were identified, including ten reported mutations and four novel mutations. Furthermore, one novel heterozygous putative pathogenic mutation was identified in CRX (OMIM: 602225; c.284delG), and one novel homozygous nonsense mutation was identified in RGS9BP (OMIM 607814; c.211G>T (p.E71*)), which is a causative gene for bradyopsia (Table 1). Table 2 lists the novel missense mutations predicted to be pathogenic by using a combination of in silico prediction tools. Gene reference numbers are shown in Appendix 2. Figure 1 shows the pedigrees of the 12 families carrying the pathogenic mutations, and the phenotype data of these patients are shown in Appendix 3 and Figure 2, Figure 3, and Figure 4.


Next-generation sequencing-based comprehensive molecular analysis of 43 Japanese patients with cone and cone-rod dystrophies.

Oishi M, Oishi A, Gotoh N, Ogino K, Higasa K, Iida K, Makiyama Y, Morooka S, Matsuda F, Yoshimura N - Mol. Vis. (2016)

Pedigrees of the 12 patients with cone or cone-rod dystrophy carrying pathogenic mutations. The patients’ IDs and the corresponding genes are shown above the pedigrees; +: wild-type allele.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4764614&req=5

f1: Pedigrees of the 12 patients with cone or cone-rod dystrophy carrying pathogenic mutations. The patients’ IDs and the corresponding genes are shown above the pedigrees; +: wild-type allele.
Mentions: Pathogenic mutations were identified in 12 of the 43 patients (27.9%). A total of 14 distinct mutations were identified, including ten reported mutations and four novel mutations. Furthermore, one novel heterozygous putative pathogenic mutation was identified in CRX (OMIM: 602225; c.284delG), and one novel homozygous nonsense mutation was identified in RGS9BP (OMIM 607814; c.211G>T (p.E71*)), which is a causative gene for bradyopsia (Table 1). Table 2 lists the novel missense mutations predicted to be pathogenic by using a combination of in silico prediction tools. Gene reference numbers are shown in Appendix 2. Figure 1 shows the pedigrees of the 12 families carrying the pathogenic mutations, and the phenotype data of these patients are shown in Appendix 3 and Figure 2, Figure 3, and Figure 4.

Bottom Line: Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia.Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD.The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

ABSTRACT

Purpose: To investigate the efficacy of targeted exome sequencing for mutational screening of Japanese patients with cone dystrophy (CD) or cone-rod dystrophy (CRD).

Methods: DNA samples from 43 Japanese patients with CD or CRD were sequenced using an exome-sequencing panel targeting all 193 known inherited eye disease genes and next-generation sequencing methodologies. Subsequently, candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed using distinct filtering approaches, which included the frequency of the variants in normal populations, in silico prediction tools, and cosegregation.

Results: Causative mutations were detected in 12 patients with CD or CRD (27.9%). In total, 14 distinct mutations were identified in the genes ABCA4, CDHR1, CRB1, CRX, GUCY2D, KCNV2, PROM1, PRPH2, and RDH5, including four novel mutations, c.3050+1G>A in ABCA4, c.386A>G in CDHR1, c.652+1_652+4del in CRB1, and c.454G>A in KCNV2. Moreover, a putative pathogenic mutation was identified in RGS9BP, a gene recognized as the source of bradyopsia.

Conclusions: Targeted exome sequencing effectively identified causative mutations in Japanese patients with CD or CRD. The results confirmed the heterogeneity of the genes responsible for CD and CRD in Japanese populations, as well as the efficacy of targeted exome sequencing-based screening of patients with inherited retinal degeneration.

No MeSH data available.


Related in: MedlinePlus