title: Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling.
abstract: X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6-20%; RPGR: 78.4% vs. 55-90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years.
authors.affiliation: Unité de Recherches Génétique et Epigénétique des Maladies Métaboliques, Neurosensorielles et du Développement, Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U781, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pelletier
authors.forename: Marguerite
authors.initials: M
authors.lastname: Jambou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delphin
authors.forename: Elena
authors.initials: E
authors.lastname: Zinovieva
authors.forename: Morgane
authors.initials: M
authors.lastname: Stum
authors.forename: Nadine
authors.initials: N
authors.lastname: Gigarel
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Christian
authors.initials: C
authors.lastname: Hamel
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dufier
authors.forename: Olivier
authors.initials: O
authors.lastname: Roche
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
mesh_terms: D002648:Child; D003663:Decision Trees; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D019204:GTP-Binding Proteins; D005817:Genetic Counseling / Q000379:methods*; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000523:psychology; D008040:Genetic Linkage; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells / Q000002:abnormalities; D012164:Retinal Diseases / Q000235:genetics* / Q000523:psychology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000523:psychology; D035781:Siblings
chemical_list: D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; C099929:RPGR protein, human; D019204:GTP-Binding Proteins