Targeted Next-Generation Sequencing Reveals Novel RP1 Mutations in Autosomal Recessive Retinitis Pigmentosa

Genet Test Mol Biomarkers. 2018 Feb;22(2):109-114. doi: 10.1089/gtmb.2017.0223.

Abstract

Background: Retinitis pigmentosa (RP) is a group of rare inherited retinal dystrophies that result in a progressive loss of vision. Molecular diagnosis of RP is difficult due to its phenotypic and genetic heterogeneities.

Aims: To investigate causative genetic mutations in a collection of RP cases: one Indian and two Chinese families with autosomal-recessive RP and two sporadic patients with RP.

Materials and methods: A total of 163 genes, which have previously been found to be involved in inherited retinal disorders, were selected for targeted next-generation sequencing (NGS). Stringent NGS data analyses followed by confirmation using Sanger sequencing and segregation analyses were applied to evaluate all identified pathogenic mutations.

Results: Four novel frameshift mutations and two compound heterozygous mutations were identified in RP1. In addition, all mutations were found to co-segregate with the disease in the three familial cases; none of the mutations were detected in control samples.

Conclusion: This study expands the mutational spectrums of RP1 for RP.

Keywords: RP1; autosomal recessive retinitis pigmentosa; targeted NGS.

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microtubule-Associated Proteins
  • Middle Aged
  • Mutation*
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*

Substances

  • Eye Proteins
  • Microtubule-Associated Proteins
  • RP1 protein, human