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 PDE6B 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.R74 C and p.T604I) in PDE6B 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 PDE6B contribute to the genetic heterogeneity of RP.
AIM: To identify the mutations in RS1 gene associated with typical phenotype of X-linked juvenile retinoschisis(XLRS) and a rare condition of concomitant glaucoma. ·METHODS: Complete ophthalmic examinations were performed in the proband. The coding regions of the RS1 gene that encode retinoschisin were amplified by polymerase chain reaction and directly sequenced. ·RESULTS: The proband showed a typical phenotype of XLRS with large peripheral retinal schisis in both eyes,involving the macula and combined with foveal cystic change,reducing visual acuity. A typical phenotype of recurrent glaucoma with high intraocular pressure(IOP) and reduced visual field was also demonstrated with the patient. Mutation analysis of RS1 gene revealed R102W(c.304C>T) mutations in the affected male,and his mother was proved to be a carrier with the causative mutation and another synonymous polymorphism(c.576C>CT). ·CONCLUSION: We identified the genetic variations of a Chinese family with typical phenotype of XLRS and glaucoma. The severe XLRS phenotypes associated with R102W mutations reveal that the mutation determines a notable alteration in the function of the retinoschisin protein. Identification of the disease-causing mutation is beneficial for future clinical references.
Xiu-Feng HuangChang-Sen TuDong-Jun XingDe-Kang GanGe-Zhi XuZi-Bing Jin
