Abstract
BackgroundPanel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa.MethodsA total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel‐based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination.ResultsOf the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0–65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands.ConclusionPanel‐based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China.
Highlights
Retinitis pigmentosa (RP, MIM#500004) is the most common group of disorder in retinal diseases, with a common manifestation of progressive photoreceptor cells and loss of retinal pigment epithelial function
Despite the development of targeted sequencing screening strategies for identifying known genes associated with RP, it is estimated that 40% of cases are still not molecularly diagnosed, indicating that there are still many novel mutations in known disease-causing genes and novel retinitis pigmentosa diseases-causative gene not found (Ellingford et al, 2016)
Of the 23 retinitis pigmentosa families included in the study, 17 probands had clinical manifestations of concurrent lens opacities, and the posterior subcapsular opacities was predominant, suggesting that posterior subcapsular cataracts is the commonest forms of retinitis pigmentosa combined with complication cataract
Summary
Retinitis pigmentosa (RP, MIM#500004) is the most common group of disorder in retinal diseases, with a common manifestation of progressive photoreceptor cells and loss of retinal pigment epithelial function. The main symptoms include night blindness, progressive reduction of visual field, and tubular vision and blindness. It is the most common blinding monogenic hereditary fundus disease with a prevalence of approximately 1/3,500– 1/5,000 (Galan et al, 2011). Despite the development of targeted sequencing screening strategies for identifying known genes associated with RP, it is estimated that 40% of cases are still not molecularly diagnosed, indicating that there are still many novel mutations in known disease-causing genes and novel retinitis pigmentosa diseases-causative gene not found (Ellingford et al, 2016). The characteristics and clinical manifestations of retinitis pigmentosa in the northeast Chinese population were analyzed, which provided assistance for subsequent clinical diagnosis and genetic counseling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
