Novel mutations in PDE6B causing human retinitis pigmentosa

• 作者: Fa-Yu Yang Feng Gu Jia Qu Jie Tian Jin-Ling Xu Lu-Lu Cheng Qing-Jie Min Ru-Yi Han Si-Si Zheng Xiang-Lian Ge Xin-Ping Yu Ye-Wen Lin Yi-Han Zheng
• 来源期刊: 国际眼科杂志：英文版
• 学科: 医学
• 关键词: compound HETEROZYGOSITY RETINITIS pigmentosa MUTATION CAPTURE next generation SEQUENCING PDE6B
• 年，卷（期）: 2016,（8）
• 页码范围: 1094-1099
• 页数: 0页
• 分类号: R774.1

摘要

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.