Patients with Retinitis Pigmentosa due to RP1 Mutations Show Greater Severity in Recessive than in Dominant Cases
|Estèle Lafont1,2,3#, Gaël Manes1,2,3#, Audrey Sénéchal1,2,3, Béatrice Bocquet1,2,3, Delphine Coustès-Chazalette4, Corinne Baudoin4, Mohamed Ksantini1,2,3, Jérôme Bourien1,2,3, Aurore Devos5, Hélène Dollfus6, Xavier Zanlonghi7, Isabelle Meunier1,2,3,4, Claire-Marie Dhaenens5, Christian P. Hamel1,2,3,4* and the French research group for autosomal dominant retinitis pigmentosa (Isabelle Audo8, Francine Behar-Cohen9, Sabine Defoort-Dhellemmes10, Jean-Louis Dufier11, Hubert Journel12, Josseline Kaplan11, Guylène Le Meur13, Saddek Mohand-Saïd8, Sylvie Odent12, Valérie Pelletier6, Bernard Puech10, Jean-Michel Rozet11, José Alain Sahel8, Michel Weber13 and Christina Zeitz8)|
|1INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France|
|2Université Montpellier 1, Montpellier, France|
|3Université Montpellier 2, Montpellier, France|
|4Genetics of Sensory Diseases, CHRU, Montpellier, France|
|5Biochemistry and Molecular Biology Department (Genopathy unit), CHRU, Lille, France|
|6Rare Genetic Ocular Diseases, CHRU, Strasbourg, France|
|7ElectroDiagnostic Imaging Unit, Clinique Sourdille, Nantes, France|
|8Inherited Retinal Dystrophies, Hôpital des 15/20, Paris, France|
|9Department of Ophthalmology, Hôtel-Dieu, Paris, France|
|10Department of Visual Investigations, CHRU, Lille, France|
|11Ophthalmic Genetics, INSERM U781, Paris, France|
|12Department of Medical Genetics, CHRU, Rennes, France|
|13Department of Ophthalmology, CHRU, Nantes, France|
|#Contributed equally to this work|
|Corresponding Author :||Christian P. Hamel
INSERM U1051, Institut des Neurosciences de Montpellier
Hôpital Saint-Eloi, BP 7410380
rue Augustin Fliche 34091 Montpellier Cedex 5, France
Tél: (33) 499 636 010
Fax: (33) 499 636 020
E-mail: [email protected]
|Received October 29, 2011; Accepted December 01, 2011; Published December 02, 2011|
|Citation: Lafont E, Manes G, Sénéchal A, Bocquet B, Coustès-Chazalette D, et al. (2011) Patients with Retinitis Pigmentosa due to RP1 Mutations Show Greater Severity in Recessive than in Dominant Cases. J Clinic Experiment Ophthalmol 2:194. doi:10.4172/2155-9570.1000194|
|Copyright: © 2011 Lafont E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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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.