Journal of Clinical and Experimental Ophthalmology
Open Access

Abstract

Patients with Retinitis Pigmentosa due to RP1 Mutations Show Greater Severity in Recessive than in Dominant Cases

Estèle Lafont, Gaël Manes, Audrey Sénéchal, Béatrice Bocquet, Delphine Coustès-Chazalette, Corinne Baudoin, Mohamed Ksantini, Jérôme Bourien, Aurore Devos, Hélène Dollfus, Xavier Zanlonghi, Isabelle Meunier, Claire-Marie Dhaenens, Christian P. Hamel, Isabelle Audo, Francine Behar-Cohen, Sabine Defoort-Dhellemmes, Jean-Louis Dufier, Hubert Journel, Josseline Kaplan, Guylène Le Meur, Saddek Mohand-Saïd, Sylvie Odent, Valérie Pelletier, Bernard Puech, Jean-Michel Rozet, José Alain Sahel, Michel Weber and Christina Zeitz

Study background: RP1 is a major gene for autosomal dominant retinitis pigmentosa and was reported in a few recessive families. Taken together, patients with RP1 mutations of both types of inheritance show a large spectrum in the severity of the disease. To get better insight in these clinical variations, patients with dominant and recessive retinitis pigmentosa due to RP1 mutations were investigated and their clinical features were compared.
Methods: RP1 exons 2 and 3 were sequenced in 324 unrelated patients with presumed recessive retinitis pigmentosa (213 simplex, 68 multiplex) or cone rod dystrophy (27 simplex, 16 multiplex) and RP1 exon 4 hot spot (nt 1500-3216) was sequenced in 174 probands with dominant retinitis pigmentosa. Visual acuity and visual field were correlated with age using Pearson’s linear coefficient and compared with a non parametric Wilcoxon test.
Results: Two novel recessive null mutations (p.His31GlnfsX47, p.Val157TrpfsX16) were found in exon 2. Five novel dominant mutations (p.Lys673ArgfsX9, p.Tyr685X, p.Ile725TyrfsX13, p.Asn748IlefsX15, p.Ser862X) and the recurrent p.Gln679X and p.Ser911X mutations were found in exon 4. In recessive cases, decrease in visual acuity was at 21.8±5.8 years with visual acuity of 0.32±0.28. In dominant cases, decrease in visual acuity occurred later at 45.2±10.4 years in one group (0.54±0.28) and at 61.0±5.2 years in a second group (0.71±0.14). Visual field decrease was noticed earlier in recessive than in dominant cases (20.9±7.2 vs 49.0±16.3) but decrease level was similar (41.8±33.3% vs 34.5±31.7%). The rate of decrease was similar for visual acuity while for visual field it was higher in recessive than in dominant cases (3.93% per year vs 1.65% per year).
Conclusions: The recessive patients had much more severe disease than dominant patients, with higher decrease rate in visual field and earlier onset in visual acuity decrease.