Author:
Audo Isabelle,Bujakowska Kinga,Mohand-Saïd Saddek,Lancelot Marie-Elise,Moskova-Doumanova Veselina,Waseem Naushin H,Antonio Aline,Sahel José-Alain,Bhattacharya Shomi S,Zeitz Christina
Abstract
Abstract
Background
Rod-cone dystrophies are heterogeneous group of inherited retinal disorders both clinically and genetically characterized by photoreceptor degeneration. The mode of inheritance can be autosomal dominant, autosomal recessive or X-linked. The purpose of this study was to identify mutations in one of the genes, PRPF31, in French patients with autosomal dominant RP, to perform genotype-phenotype correlations of those patients, to determine the prevalence of PRPF31 mutations in this cohort and to review previously identified PRPF31 mutations from other cohorts.
Methods
Detailed phenotypic characterization was performed including precise family history, best corrected visual acuity using the ETDRS chart, slit lamp examination, kinetic and static perimetry, full field and multifocal ERG, fundus autofluorescence imaging and optic coherence tomography. For genetic diagnosis, genomic DNA of ninety families was isolated by standard methods. The coding exons and flanking intronic regions of PRPF31 were PCR amplified, purified and sequenced in the index patient.
Results
We showed for the first time that 6.7% cases of a French adRP cohort have a PRPF31 mutation. We identified in total six mutations, which were all novel and not detected in ethnically matched controls. The mutation spectrum from our cohort comprises frameshift and splice site mutations. Co-segregation analysis in available family members revealed that each index patient and all affected family members showed a heterozygous mutation. In five families incomplete penetrance was observed. Most patients showed classical signs of RP with relatively preserved central vision and visual field.
Conclusion
Our studies extended the mutation spectrum of PRPF31 and as previously reported in other populations, it is a major cause of adRP in France.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Reference31 articles.
1. Birch DG, Fish GE: Rod ERGs in retinitis pigmentosa and cone-rod degeneration. Invest Ophthalmol Vis Sci. 1987, 28: 140-150.
2. Carter-Dawson LD, LaVail MM, Sidman RL: Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci. 1978, 17: 489-498.
3. Cideciyan AV, Hood DC, Huang Y, Banin E, Li ZY, Stone EM, Milam AH, Jacobson SG: Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc Natl Acad Sci USA. 1998, 95: 7103-7108. 10.1073/pnas.95.12.7103.
4. Milam AH, Li ZY, Fariss RN: Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res. 1998, 17: 175-205. 10.1016/S1350-9462(97)00012-8.
5. Hartong DT, Berson EL, Dryja TP: Retinitis pigmentosa. Lancet. 2006, 368: 1795-1809. 10.1016/S0140-6736(06)69740-7.
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