Unravelling the genetic basis of simplex Retinitis Pigmentosa cases.
Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families.
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
Nereida
N
Bravo-Gil
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
María
M
González-Del Pozo
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
Marta
M
Martín-Sánchez
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
Cristina
C
Méndez-Vidal
Department of Ophthalmology, University Hospitals Virgen Macarena and Virgen del Rocío, Seville, Spain.|Retics Patologia Ocular, OFTARED, Instituto Salud Carlos III, Madrid, Spain.
Enrique
E
Rodríguez-de la Rúa
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
Salud
S
Borrego
Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
Guillermo
G
Antiñolo
D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*