Phenotypic Variability and Long-term Follow-up of Patients With Known and Novel PRPH2/RDS Gene Mutations

Renner, Agnes B.; Fiebig, Britta; Weber, Bernhard H. F.; Wissinger, Bernd; Andréasson, Sten; Gal, Andreas; Cropp, Elke; Kohl, Susanne; Kellner, Ulrich

doi:10.1016/j.ajo.2008.09.007

Cited by 71 publications

(47 citation statements)

References 32 publications

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“…This finding is consistent with that in a previous study where patients with PRPH2 mutations exhibited different phenotypes. 19 The previous studies showed a wide range of phenotypic expression from the same mutation: central areolar choroidal dystrophy, autosomal dominant RP, adult vitelliform macular dystrophy, and cone-rod dystrophy.…”

Section: Discussionmentioning

confidence: 99%

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

Miyata

Ogino

Gotoh

et al. 2016

Eye

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Purpose To evaluate whether the length of the inner segment ellipsoid (ISe) band can be used as a prognostic factor for disease course in retinitis pigmentosa (RP) patients with EYS mutations by observation over a period of 5 years. Methods Twelve RP patients with EYS mutations were studied. The horizontal and vertical ISe length of the right eye was manually measured at five time points annually, using spectral domain optical coherence tomography. A regression line through the five points from baseline to the final measurement was drawn and the ratio of the length (%) at each point to the baseline length was calculated; the slope was defined as the rate of ISe shortening (%/year). The correlation between the rate of ISe shortening and age, visual acuity, and mean deviation (MD) value were evaluated. The intraclass correlation coefficient (ICC) for the measurements was calculated. Results The mean rate of ISe shortening was − 4.65 ± 2.89% per year and the decline was statistically significant. The rate of shortening was significantly negatively correlated with the baseline length (P = 0.046, r = 0.58), but not with the baseline age, visual acuity, and MD value. The ICC (2, 1) was 0.999. Conclusions ISe of all RP patients with EYS mutations shortened during the 5 years of annual observation. The measurement of the length of ISe is a simple and convenient method with high repeatability, and the length is a sensitive prognostic factor for the rate of ISe shortening in RP patients with EYS mutations.

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Section: Discussionmentioning

confidence: 99%

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

Miyata

Ogino

Gotoh

et al. 2016

Eye

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“…Mutations in PRPH2 or RDS have been identified in 20% of patients with adult vitelliform macular dystrophy (Felbor et al, 1997). PRPH2 mutations are also associated with various retinal and macular dystrophies (Renner et al, 2009;Coco et al, 2010). Of the 10 patients (9 probands) referred for gene testing, a previously reported heterozygous mutation c.514C>T, p.Arg172Trp (Weleber et al, 1993) was identified in 1 proband with dominant macular dystrophy, and a novel heterozygous mutation c.4G>T, p.Ala2Ser was detected in another male proband (Tables 2 and 3).…”

Section: Dominantly Inherited Diseasesmentioning

confidence: 99%

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses

Ramkumar

Gudiseva

Kishaba

et al. 2017

Genetic Testing and Molecular Biomarkers

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Aim: To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). Methods: After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Results: Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Conclusions: Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

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“…Although AVMD can be distinguished from BVMD in most cases by its later onset, smaller lesion, slower progression, and normal or slightly subnormal electro-oculogram [14], these 2 diseases can have overlapping clinical features such as the round yellowish lesion and the inheritance pattern. Several studies have found mutations in BEST1 , PRPH2 , IMPG1 , or IMPG2 genes in a minority of AVMD cases and may be inherited in an autosomal dominant manner [4,8,15]. To date, 9 mutations in the BEST1 gene have been found in AVMD, 2 (p.Ala243Val, p.Thr6Pro) of which have also been reported in BVMD [8,16].…”

Section: Discussionmentioning

confidence: 99%

Novel <b><i>BEST1</i></b> Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy

Liu

Zhang²,

Xuan³

et al. 2016

Ophthalmic Res

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Purpose: To describe the clinical features and to analyze BEST1 mutations in patients with Best vitelliform macular dystrophy (BVMD). Methods: Thirteen individuals affected by BVMD from 6 unrelated Chinese families were studied. Complete ophthalmological examinations were performed, and the BEST1 gene was screened in all participants and 100 controls. Follow-ups were arranged within 12 months. Results: All 6 probands showed typical fundus appearances of BVMD. One of the 6 had a history of angle closure glaucoma, and another showed a unilateral focal choroidal excavation on optical coherence tomography. One patient experienced progression of the macular lesion during the follow-up. The asymptomatic mutation carriers had normal fundus but abnormal Arden ratios on electro-oculograms. Besides 4 previously reported mutations (p.Ser16Phe, p.Ser144Asn, p.Glu292Lys, p.Glu300Lys), 2 novel disease-causing mutations (p.Thr307Asp, p.Arg47His) were identified, of which p.Arg47His has been reported in adult-onset vitelliform macular dystrophy. Conclusions: Our findings have expanded the mutational and clinical spectrum of BVMD in a Chinese population. Clinical presentations of angle closure glaucoma and/or focal choroidal excavation may be related to BVMD, underlining the necessity of multimodal studies and risk assessment of angle closure glaucoma in BEST1 mutation carriers. BVMD and adult-onset vitelliform macular dystrophy may share a common etiology in some cases.

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Phenotypic Variability and Long-term Follow-up of Patients With Known and Novel PRPH2/RDS Gene Mutations

Cited by 71 publications

References 32 publications

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

Inner segment ellipsoid band length is a prognostic factor in retinitis pigmentosa associated with EYS mutations: 5-year observation of retinal structure

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses

Novel <b><i>BEST1</i></b> Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy

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