Introduction: Retinitis pigmentosa (RP), a hereditary heterogeneous disease with a prevalence of 1/4000, characterized by the degeneration of photoreceptors leading to progressive loss of vision in patients. We have identi fi ed a three-generation X-linked RP family. Materials and Methods: Eighteen X chromosome microsatellite markers were used to locate disease locus, and one of the Sibling-pairs within the family were used to performed Whole-exome sequencing. Results: The disease locus was mapped between markers DXS1068 and DXS1196. Whole-exome sequencing identifi ed 139 possible SNPs located within the critical diseasescausing intervals. Considering that co-segregation of mutation and genes expression patterns, the RP2_c.102G> A point mutation might be the responsible mutation of this family's disease. It is a novel allele of RP2 gene with allele frequency <1%, and no known functional impact. At protein level the mutation appears to be no functional impact (Lys34> Lys), however, c.102G> A located at the last nucleotide of the splicing donor site of exon1, suggesting that this mutation might cause intron retention at the transcriptional level. A MiniGene assay was designed to validate the functional consequences of this mutation. Conclusion: We have identi fi ed a novel splicing-site mutation of RP2 gene from an X-Link RP family. In vitro functional analysis using MiniGene assay has been performed to verify the functional impact of the mutation.
Date:
2019-07
Relation:
European Journal of Human Genetics. 2019 Jul;27:68.
