Spectrum of Rhodopsin Mutations in French Autosomal Dominant Rod–Cone Dystrophy Patients

Audo, Isabelle; Manes, Gae͏̈l; Mohand‐Saïd, Saddek; Friedrich, Anne; Lancelot, Marie-Elise; Arnaiz‐Villena, Antonio; Moskova-Doumanova, Veselina; Poch, Olivier; Zanlonghi, Xavier; Hamel, Christian; Sahel, José‐Alain; Bhattacharya, Siladitya; Zeitz, Christina

doi:10.1167/iovs.09-4766

Cited by 45 publications

(32 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vice versa, our most common mutation in RHO does not appear in France (Table 2). However, one Rho mutation, RHO c.403C>G (p.Arg135Gly), was previously reported by Audo et al 29 with a single base-pair difference (c.403C>T (p.Arg135Trp); we believe that this can result from a hypermutable site. This finding suggests that most mutations arose after the migration and confirms the uniqueness of the founder effect on the French Canadian population of Quebec.…”

Section: Discussionmentioning

confidence: 50%

“…13 j 8302 specifically found in French families from France. The most common French mutation in adRP, which is RHO c.1040C>T (p.Pro347Leu), 29 does not appear in our Quebec cohort. Vice versa, our most common mutation in RHO does not appear in France (Table 2).…”

Section: Discussionmentioning

confidence: 53%

“…The same authors found that Pro347Leu is the most common mutation in RHO, which was the most common casual gene in French adRP patients, representing 16.5%. 29 The PRPH2, which was mainly present in population of European ancestry, accounted for up to 9% of all adRP mutations. [9][10][11] Of interest for population genetics is the fact that none of our identified adRP mutations and none of the reported mutations could be directly traced back to the 1608 French settlers.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population

Coussa

Chakarova²,

Ajlan

et al. 2015

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

PURPOSE.The French Canadian population of Quebec is a unique, well-known founder population with religious, linguistic, and geographic isolation. The genetics of retinitis pigmentosa (RP) in Quebec is not well studied thus far. The purpose of our study was to establish the genetic architecture of autosomal dominant RP (adRP) and to characterize the phenotypes associated with new adRP mutations in Quebec.METHODS. Sanger sequencing of the commonly mutated currently known adRP genes was performed in a clinically well-characterized cohort of 60 adRP French Canadian families. Phenotypes were analyzed by projected visual acuity (best corrected), Goldmann visual fields, optical coherence tomography (OCT), fundus autofluorescence (FAF), and ERG. The potential effect of the novel mutations was assessed using in silico bioinformatic tools. The pathogenicity of all variants was then confirmed by segregation analysis within the families, when available. RESULTS.We identified the causal mutation/gene in 24 of our adRP families, as 24 (40%) of 60 patients had adRP mutations in six known adRP genes. Eleven (46%) of these mutations were in RHO, four mutations (17%) were found in SNRNP200, three mutations (12.5%) in PRPH2/RDS, three mutations (12.5%) in TOPORS, two mutations (8%) in PRPF31, and one mutation (4%) in IMPDH1. Four mutations were novel. We identified new mutations in RHO (p.S270I), PRPF31 (p.R288W), IMPDH1 (p.Q318H), and TOPORS (p.H889R); the rest were previously reported. We present the genotype-phenotype characteristics of the four novel missense mutations.CONCLUSIONS. This is the first large screening of adRP genes in the founder population of Quebec. Our prevalence of known adRP genes is 40% in the French Canadian population, which is lower than in other adRP populations around the world, illustrating the uniqueness of the French Canadian population. Our findings are crucial in expanding the current understanding of the genotypic-phenotypic spectrum of RP and documenting the genetic architecture of our founder population.

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population

Coussa

Chakarova²,

Ajlan

et al. 2015

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Full-field ERG remains the gold standard to differentiate these conditions; however, it can be difficult to perform in young children, which may result in poor traces with significantly decreased informative value. DNA testing is increasingly useful, but the causative mutation is still not found in most RP or CSNB patients, 21–24 and screening may take several months. DNA testing also can be costly; therefore, imaging tests that can aid in the accuracy of the initial diagnosis could save the patient and institution from ordering studies aimed at the wrong condition.…”

Section: Discussionmentioning

confidence: 99%

Autofluorescence Imaging and Spectral-Domain Optical Coherence Tomography in Incomplete Congenital Stationary Night Blindness and Comparison With Retinitis Pigmentosa

Chen

Greenberg

Lazow

et al. 2012

American Journal of Ophthalmology

View full text Add to dashboard Cite

PURPOSE To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. DESIGN Prospective cross-sectional study. METHODS Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. RESULTS Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive CSNB2 had a mutation, p.R614X, in the gene encoding calcium channel, α 1F subunit. CONCLUSIONS CSNB2 patients (X-linked recessive and autosomal recessive) had significantly thinner retinas than myopic controls. However, they demonstrated qualitatively normal SD OCT and FAF images, and therefore can be differentiated from RP patients with these techniques. Although ERG testing remains the gold standard for the diagnosis of these conditions, FAF and SD OCT systems are more widely available to community ophthalmologists, offer shorter acquisition times, and, unlike ERG, can be performed on the same day as the initial clinic visit. Therefore, as a supplement to ERG and genetic testing, we advocate the use of FAF and SD OCT in the examination of patients with CSNB2 and RP.

show abstract

“…This represents a distinct phenotype, which is usually associated with autosomal dominant RP linked to mutations in the rhodopsin gene (RHO; MIM# 180380) (Heckenlively et al 1991) (Audo et al 2010).…”

Section: Genotype-phenotypic Characterizationmentioning

confidence: 99%

EYS is a major gene for rod-cone dystrophies in France

et al. 2010

Self Cite

View full text Add to dashboard Cite

Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of 239 sporadic and arRP French cases. Direct sequencing of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology. We mostly identified novel mutations in EYS in a total of 29 patients: Fifteen of the mutations were predicted to create premature stop codons and two represent exonic deletions. In addition, twenty missense, silent or splice-site mutations were detected. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a single mutation. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina suggesting potential phenotypic variability. With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere.

show abstract

Spectrum of Rhodopsin Mutations in French Autosomal Dominant Rod–Cone Dystrophy Patients

Cited by 45 publications

References 35 publications

Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population

Genotype and Phenotype Studies in Autosomal Dominant Retinitis Pigmentosa (adRP) of the French Canadian Founder Population

Autofluorescence Imaging and Spectral-Domain Optical Coherence Tomography in Incomplete Congenital Stationary Night Blindness and Comparison With Retinitis Pigmentosa

EYS is a major gene for rod-cone dystrophies in France

Contact Info

Product

Resources

About