Assignment of a Gene for Autosomal Recessive Retinitis Pigmentosa (RP12) to Chromosome 1q31-q32.1 in an Inbred and Genetically Heterogeneous Disease Population

Soest, S. van; Born, L. I. Van Den; Gál, A.; Farrar, G. Jane; Bleeker-Wagemakers, Liesbeth M.; Westerveld, A.; Humphries, Peter; Sandkuijl, L. A.; Bergen, Arthur A. B.

doi:10.1006/geno.1994.1422

Cited by 99 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A possible explanation for our results is that the Gly367Arg substitution is causative of the disease phenotype in those individuals with this amino acid change and that some as yet unidentified locus is responsible for the disease phenotype in II-6 and his affected offspring III-7 and III-9. If POAG were a rare disease, this situation would be unlikely (although not impossible; a linkage to 1q has been found in part, but not all, of a Dutch pedigree segregating recessive RP (van Soest et al, 1994). The incidence of POAG, however, is relatively high; it has been estimated to affect 1-2% of the population at large.…”

Section: Discussionmentioning

confidence: 89%

Novel mutations in the TIGR gene in early and late onset open angle glaucoma

et al. 1998

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 89%

Novel mutations in the TIGR gene in early and late onset open angle glaucoma

et al. 1998

Self Cite

View full text Add to dashboard Cite

“…Thirty-four patients were part of a large consanguineous pedigree from a genetically isolated town in The Netherlands. 23 Nine patients demonstrated simplex cases, and 12 non-GI patients were part of families with 2 to 3 affected siblings. The data that we were able to collect per patient group are represented in Table S1 (available at www.aaojournal.org).…”

Section: Resultsmentioning

confidence: 99%

Genotypic and Phenotypic Characteristics of CRB1 -Associated Retinal Dystrophies

et al. 2017

View full text Add to dashboard Cite

Purpose: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies.Design: Retrospective cohort study. Participants: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. Methods: A medical record review of 55 patients for age at onset, medical history, initial symptoms, bestcorrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography.Main Outcome Measures: Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings.Results: A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0e55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P ¼ 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rodecone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients.Conclusions: Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life. Ophthalmology 2017;124:884-895 ª 2017 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org.Mutations in the CRB1 gene are associated with a wide variety of severe retinal dystrophies with variable phenotypes, including panretinal dystrophies such as retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), and coneerod dystrophy, as well as central phenotypes such as isolated macular dystrophy and foveal retinoschisis. Retinitis pigmentosa is a clinically and genetically heterogeneous disorder. Mutations in the CRB1 gene have been associated with RP12, a distinct form of RP characterized by preservation of para-arteriolar retinal pigment epithelium, progressive visual field (VF) loss starting from the first decade of life, and early macular involvement. 4 Other common features are hyperopia and optic disc drusen, previously described in a Dutch genetic isolate (GI). 5Classic forms of earl...

show abstract

“…This genetic heterogeneity has been reported in numerous other examples from the Tunisian population [17,18] as well as in other populations [19,20]. Locus heterogeneity within the same consanguineous pedigree represents one of the important pitfalls in the homozygosity mapping strategy.…”

Section: Resultsmentioning

confidence: 92%