AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal dise...AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal diseases were scanned with capture next generation sequencing (CNGS) approach. Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE5B mutations based on the available two public exome databases (1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated. RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A (p.W378X) and c.2395C>T (p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations (p.R74C and p.T6041) in PDE5B have relatively high frequencies in the ESP6500 and in-house databases, respectively, while no common dominant mutation in each of the database or across all databases. CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE9B contribute to the genetic heterogeneity of RP.展开更多
患者女,54岁。因双眼晚上视物模糊4年、加重2年(白天视物无异常),于2024年4月25日到成都爱迪眼科医院就诊。既往身体健康。家族中无类似疾病史。眼部检查:双眼祼眼视力1.0;右眼、左眼眼压分别为10、13 mm Hg(1 mm Hg=0.133 kPa)。双眼...患者女,54岁。因双眼晚上视物模糊4年、加重2年(白天视物无异常),于2024年4月25日到成都爱迪眼科医院就诊。既往身体健康。家族中无类似疾病史。眼部检查:双眼祼眼视力1.0;右眼、左眼眼压分别为10、13 mm Hg(1 mm Hg=0.133 kPa)。双眼眼前节未见明显异常。眼底检查,双眼视盘、视网膜色泽红润,黄斑区颜色、形态基本正常;后极部以视盘、黄斑为中心,边界清楚呈对称性环形萎缩区,色泽晦暗,其间可见骨细胞样色素沉着,萎缩区外视网膜色泽、形态未见明显异常(图1A,1B)。眼底自发荧光(FAF)检查,双眼病灶呈边界清晰的弱荧光区(图1C,1D)。光相干断层扫描(OCT)检查,双眼环形萎缩区椭圆体带(EZ)连续性中断,视网膜色素上皮(RPE)层萎缩、变薄和不规则,脉络膜层厚度明显变薄(图1E,1F);周边视网膜EZ正常。全视野视网膜电图(ERG)检查,各波形态正常,仅部分波形振幅不同程度降低(图2)。30°视野检查,双眼呈与萎缩区相吻合的对称性巨大环形暗点(图3)。OCT血管成像(OCTA)检查,双眼萎缩区视网膜全层血流密度无明显改变;脉络膜中小毛细血管层可见边界清楚的萎缩区域,血管床密度、血流量降低;脉络膜大血管层受累相对较轻,血管床密度、血流量重度降低(图4)。患者母亲、兄妹、女儿均否认夜盲史。其中母亲眼底检查正常。女儿眼前节、眼底视网膜色泽、脉络膜全层结构和血流量未见异常。临床诊断:双眼色素性视网膜炎(RP)可能。展开更多
AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and preve...AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic.METHODS:The Vldlr^(-/-)mice,the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene,with the rd1 mice,the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred.Intercrossing of the above two mice led to the birth of the F1 hybrids,further inbreeding of which gave birth to the F2 offspring.The ocular genotypes and phenotypes of the mice from all generations were examined,with the F2 offspring grouped according to the genotypes.RESULTS:The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function.The Vldlr^(-/-)mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography.The F1 hydrides,with the heterozygote genotype,exhibited no phenotypes of RP or retinal NV.The F2 offspring with homozygous genotypes were grouped into four subgroups.They were the F2-Ⅰmice with the wild-type Pde6b and Vldlr genes(Pde6b~(+/+)-Vldlr~(+/+)),which had normal ocular phenotypes;the F2-Ⅱmice with homozygous mutant Vldlr gene(Pde6b~(+/+)-Vldlr^(-/-)),which exhibited the retinal NV phenotype;the F2-Ⅲmice with homozygous mutant Pde6b gene(Pde6b^(-/-)-Vldlr~(+/+)),which exhibited the RP phenotype.Specifically,the F2-Ⅳmice with homozygous mutant Vldlr and Pde6b gene(Pde6b^(-/-)-Vldlr^(-/-))showed only the RP phenotype,without the signs of retinal NV.CONCLUSION:The retinal NV can be inhibited by the RP phenotype,which implies the role of a hyperoxic state in treating retinal NV diseases.展开更多
基金Supported by the Chinese National Program on Key Basic Research Project(973 Program,No.2013CB967502)the Natural Science Foundation of China(No.81201181/H1818)+2 种基金Zhejiang Provincial&Ministry of Health Research Fund for Medical Sciences(No.2016KYA145)Wenzhou City Grant(No.Y20140633)Chinese National Training Programs of Innovation and Entrepreneurship for Undergraduates(No.20130343005)
文摘AIM: To identify the genetic defects of a Chinese patient with sporadic retinitis pigmentosa (RP). METHODS: Ophthalmologic examinations were performed on the sporadic RP patient, 144 genes associated with retinal diseases were scanned with capture next generation sequencing (CNGS) approach. Two heterozygous mutations in PDE6B were confirmed in the pedigree by Sanger sequencing subsequently. The carrier frequency of PDE6B mutations of reported PDE5B mutations based on the available two public exome databases (1000 Genomes Project and ESP6500 Genomes Project) and one in-house exome database was investigated. RESULTS: We identified compound heterozygosity of two novel nonsense mutations c.1133G>A (p.W378X) and c.2395C>T (p.R799X) in PDE6B, one reported causative gene for RP. Neither of the two mutations in our study was presented in three exome databases. Two mutations (p.R74C and p.T6041) in PDE5B have relatively high frequencies in the ESP6500 and in-house databases, respectively, while no common dominant mutation in each of the database or across all databases. CONCLUSION: We demonstrates that compound heterozygosity of two novel nonsense mutations in PDE6B could lead to RP. These results collectively point to enormous potential of next-generation sequencing in determining the genetic etiology of RP and how various mutations in PDE9B contribute to the genetic heterogeneity of RP.
文摘患者女,54岁。因双眼晚上视物模糊4年、加重2年(白天视物无异常),于2024年4月25日到成都爱迪眼科医院就诊。既往身体健康。家族中无类似疾病史。眼部检查:双眼祼眼视力1.0;右眼、左眼眼压分别为10、13 mm Hg(1 mm Hg=0.133 kPa)。双眼眼前节未见明显异常。眼底检查,双眼视盘、视网膜色泽红润,黄斑区颜色、形态基本正常;后极部以视盘、黄斑为中心,边界清楚呈对称性环形萎缩区,色泽晦暗,其间可见骨细胞样色素沉着,萎缩区外视网膜色泽、形态未见明显异常(图1A,1B)。眼底自发荧光(FAF)检查,双眼病灶呈边界清晰的弱荧光区(图1C,1D)。光相干断层扫描(OCT)检查,双眼环形萎缩区椭圆体带(EZ)连续性中断,视网膜色素上皮(RPE)层萎缩、变薄和不规则,脉络膜层厚度明显变薄(图1E,1F);周边视网膜EZ正常。全视野视网膜电图(ERG)检查,各波形态正常,仅部分波形振幅不同程度降低(图2)。30°视野检查,双眼呈与萎缩区相吻合的对称性巨大环形暗点(图3)。OCT血管成像(OCTA)检查,双眼萎缩区视网膜全层血流密度无明显改变;脉络膜中小毛细血管层可见边界清楚的萎缩区域,血管床密度、血流量降低;脉络膜大血管层受累相对较轻,血管床密度、血流量重度降低(图4)。患者母亲、兄妹、女儿均否认夜盲史。其中母亲眼底检查正常。女儿眼前节、眼底视网膜色泽、脉络膜全层结构和血流量未见异常。临床诊断:双眼色素性视网膜炎(RP)可能。
基金Supported by the Pilot Project of Fujian Province(No.2016Y0067,No.2020Y0076,No.2020J05282)the Foundation of Key Research Plan of Shaanxi Province(No.2018SF-257)the Scientific Research Project of the 900th Hospital of Joint Logistic Support Force,PLA of 2018(No.2018Q02)。
文摘AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic.METHODS:The Vldlr^(-/-)mice,the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene,with the rd1 mice,the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred.Intercrossing of the above two mice led to the birth of the F1 hybrids,further inbreeding of which gave birth to the F2 offspring.The ocular genotypes and phenotypes of the mice from all generations were examined,with the F2 offspring grouped according to the genotypes.RESULTS:The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function.The Vldlr^(-/-)mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography.The F1 hydrides,with the heterozygote genotype,exhibited no phenotypes of RP or retinal NV.The F2 offspring with homozygous genotypes were grouped into four subgroups.They were the F2-Ⅰmice with the wild-type Pde6b and Vldlr genes(Pde6b~(+/+)-Vldlr~(+/+)),which had normal ocular phenotypes;the F2-Ⅱmice with homozygous mutant Vldlr gene(Pde6b~(+/+)-Vldlr^(-/-)),which exhibited the retinal NV phenotype;the F2-Ⅲmice with homozygous mutant Pde6b gene(Pde6b^(-/-)-Vldlr~(+/+)),which exhibited the RP phenotype.Specifically,the F2-Ⅳmice with homozygous mutant Vldlr and Pde6b gene(Pde6b^(-/-)-Vldlr^(-/-))showed only the RP phenotype,without the signs of retinal NV.CONCLUSION:The retinal NV can be inhibited by the RP phenotype,which implies the role of a hyperoxic state in treating retinal NV diseases.
