Lu-Lu Cheng1, Ru-Yi Han1, Fa-Yu Yang1, Xin-Ping Yu1, Jin-Ling Xu1, Qing-Jie Min2, Jie Tian1, Xiang-Lian Ge1, Si-Si Zheng1, Ye-Wen Lin1, Yi-Han Zheng1, Jia Qu1, Feng Gu1. 1. School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou 325027, Zhejiang Province, China. 2. Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China.
Abstract
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.R74C 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 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.R74C 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.
Authors: D Valverde; M Baiget; R Seminago; E del Rio; B García-Sandoval; T del Rio; M Bayés; S Balcells; A Martínez; D Grinberg; C Ayuso Journal: Hum Mutat Date: 1996 Impact factor: 4.878
Authors: Panagiotis I Sergouniotis; Christina Chakarova; Cian Murphy; Mirjana Becker; Eva Lenassi; Gavin Arno; Monkol Lek; Daniel G MacArthur; Shomi S Bhattacharya; Anthony T Moore; Graham E Holder; Anthony G Robson; Uwe Wolfrum; Andrew R Webster; Vincent Plagnol Journal: Am J Hum Genet Date: 2014-05-01 Impact factor: 11.025
Authors: Chunbo Yang; Maria Georgiou; Robert Atkinson; Joseph Collin; Jumana Al-Aama; Sushma Nagaraja-Grellscheid; Colin Johnson; Robin Ali; Lyle Armstrong; Sina Mozaffari-Jovin; Majlinda Lako Journal: Front Cell Dev Biol Date: 2021-07-28