A compound heterozygous mutation in the gene usherin 2A (USH2A; c.6,485+5G>A/c.11,156G>A) and a heterozygous X‑linked mutation in the gene retinitis pigmentosa 2 (RP2) ARL3 GTPase‑activating protein (RP2; c.358C>T) were identified by Sanger sequencing and co‑segregation analysis, of which the pathogenic mutation (c.6,485+5G>A) in USH2A has not been previously reported among Chinese patients.
This was further validated by reduced levels of Kif7 at cilia tips detected in fibroblasts and induced pluripotent stem cell (iPSC) 3D optic cups derived from a patient carrying an RP2 nonsense mutation c.519C > T (p.R120X), which lack detectable RP2 protein.
Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors.
Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2RP2 promoter whose 5meCpG status correlates with XCI.
X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15.
Mutations in the N-terminus of the X-linked retinitis pigmentosa protein RP2 interfere with the normal targeting of the protein to the plasma membrane.