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
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.
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.
