title: Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland.
abstract: Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive photoreceptor degeneration. An accurate molecular diagnosis is essential for disease characterization and clinical prognoses. A retinal capture panel that enriches 186 known retinal disease genes, including 55 known RP genes, was developed. Targeted next-generation sequencing was performed for a cohort of 82 unrelated RP cases from Northern Ireland, including 46 simplex cases and 36 familial cases. Disease-causing mutations were identified in 49 probands, including 28 simplex cases and 21 familial cases, achieving a solving rate of 60 %. In total, 65 pathogenic mutations were found, and 29 of these were novel. Interestingly, the molecular information of 12 probands was neither consistent with their initial inheritance pattern nor clinical diagnosis. Further clinical reassessment resulted in a refinement of the clinical diagnosis in 11 patients. This is the first study to apply next-generation sequencing-based, comprehensive molecular diagnoses to a large number of RP probands from Northern Ireland. Our study shows that molecular information can aid clinical diagnosis, potentially changing treatment options, current family counseling and management.
authors.affiliation: Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Sharon
authors.initials: S
authors.lastname: Alexander
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.forename: Colin E
authors.initials: CE
authors.lastname: Willoughby
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Zaneveld
authors.forename: Lichun
authors.initials: L
authors.lastname: Jiang
authors.forename: Zachry T
authors.initials: ZT
authors.lastname: Soens
authors.forename: Philip
authors.initials: P
authors.lastname: Earle
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Giuliana
authors.initials: G
authors.lastname: Silvestri
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D005190:Family; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009660:Northern Ireland; D057089:Pathology, Molecular; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics*