Progress in research on pathogenic genes of retinitis pigmentosa / 中华眼底病杂志

Retinitis pigmentosa (RP) is a group of hereditary blinding fundus diseases caused by abnormalities in photoreceptors of the retina.RP is highly heterogeneous in hereditary and cdinical phenotypes.It can be divided into simple type RP and syndrome type RP.The main inheritance patterns are autosomal dominant,autosomal recessive inheritance and X-linked inheritance.With the popularization and clinical application of gene sequencing technology,more and more disease-causing genes have been discovered,and these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cell.ln-depth understanding of RP pathogenic genes not only provides a theoretical basis for RP diagnosis and genetic counseling,but also provides guidance for RP gene therapy.

Genotype and clinical phenotype analysis in patients with retinitis pigmentosa and cone rod dystrophy / 中华眼底病杂志

Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD).Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study.The patient's medical history and family history were collected.All the patients and family members received complete ophthalmic examinations to determine the phenotype,including best corrected visual acuity,slit lamp microscope,indirect ophthalmoscopy,color fundus photography,optical coherence tomography,full-field electroretinogram,and fluorescein fundus angiography.DNA was abstracted from patients and family members.Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations.Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites.The relationship between genotype and clinical phenotype of RP and CORD was analyzed.Results Of the 37 patients with RP,13 were from 6 families,including 4 families with autosomal dominant inheritance,2 families with autosomal recessive inheritance,and 3 in 6 families were detected pathogenic gene mutations.24 cases were scattered RP.Six patients with CORD were from four families,all of which were autosomal recessive.Of the 43 patients,21 patients were detected the pathogenic gene mutation,and the positive rate was 48.8％.Among them,15 patients with RP were detected 10 pathogenic gene mutations including USH2A,RP1,MYO7A,C8orf37,RPGR,SNRNP200,CRX,PRPF31,C2orf71,IMPDH1,and the clinical phenotype included 10 typical RP,2 cases of RPSP,3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations,including 2 cases of ABCA4,2 mutations of RIMS 1 gene,1 case of CLN3 gene mutation,and 1 case of CRB 1 and RPGR double gene mutation.Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar.For patients with early RP and CORD,clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.

RP research in the era of precision medicine:discovery to translation / 中华实验眼科杂志

Retinitis pigmentosa (RP) encompasses many different hereditary retinal degenerations that are caused by a vast array of different gene mutations and have highly variable disease presentations and severities.Work over the past 25 years has resulted in the identification of genes responsible for about 50％ of the RP cases,and it's predicted that most of the remaining disease-causing genes will be identified by the year 2020 or most likelysooner.This marked acceleration is the result of dramatic improvements in DNA-sequencing technologies and the associated analysis.The advent of two recent innovations, induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease-9 (Cas-9) mediated genome editing,are changing the landscape of RP research, with causative genes being identified at an accelerated rate withgreat potential to translate these discoveries into personalized therapeutic strategies.

The hereditary types and clinical characteristics of 137 patients with retinitis pigmentosa in Ningxia / 中华眼底病杂志

ObjectiveTo observe the hereditary types and clinical characteristics of 137 patients with retinitis pigmentosa (RP) in Ningxia.MethodsOne hundred and thirty-seven patients with RP who diagnosed by the examinations of visual acuity, optometry, direct or indirect ophthalmoscope, visual field,optical coherence tomography (OCT) and electroretinogram were enrolled. The hereditary types and clinical characteristics were analyzed according to the family history and the results of ophthalmologic examinations.ResultsOne hundred and thirty-seven patients included 29 autosomal dominant RP (ADRP) patients from 8 families (7.4％), 16 autosomal recessive RP (ARRP) patients from 15 families (13. 9％), 10 X-linked RP (XLRP) from 3 families (2.8％), and 82 simplex RP (SRP) patients (75.9％).There were 15consanguineous marriage families out of 26 families with RP history (57.7 ％). The patients were classified as typical RP (102 patients, 74.5％) and atypical RP (35 patients, 25.5％). All the ADRP and XLRP patients showed typical clinical features of RP. Ten (62.5％) of ARRP patients and 53 (64.6％) of SRP patients had typical features of RP. Six (37.5％) of ARRP patients and 29 (35.4％) of SRP patients had atypical features of RP. Among atypical RP patients, 17 (48. 6％) patients were non-pigmented RP which including 3 patients were misdiagnosed as amblyopia during childhood. The logarithm of minimal angle of resolution (logMAR) best corrected visual acuity (BCVA) of ADRP patients was 1.04±0.51 at the age older than 51 years, while the BCVA of ARRP and XLRP patients were 0. 92+0. 61 and 1. 70±0. 02 respectively at 21 to 30 years of age. One hundred and twenty-three (89. 8%) patients suffered from varying degrees of myopia. OCT showed that the average thickness of macular fovea in ADRP patients was ( 185. 73 + 1. 23) μm at the age older than 51 years, while in ARRP and XLRP patients were (173. 21 ± 0. 98) and (170. 49+1. 15) μm respectively at 21 to 30 years of age. Conclusions ADRP and XLRP are typical RP. All atypical RP are ARRP and SRP. Non-pigmented RP are mainly seen in atypical RP which often misdiagnosed as amblyopia during childhood. The photoreceptors in macula are damaged in the early stage and the decline of visual acuity occurred at 21 to 30 years of age in patients with ARRP and XLRP. The ADRP patients has late slower decline of visual acuity and retain some visual acuity at the age older than 51 years.