Our results support the hypothesis that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations may reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1.
Eleven carriers from two families with XLRP and mutations in RPGR underwent clinical examination including fundus photography, AF, full-field electroretinography, Goldmann kinetic perimetry and two-colour threshold perimetry (2CT perimetry).
In conclusion, we reported on a family in which an asymptomatic woman with somatic-gonadal mosaicism for a RPGR gene mutation transmitted the mutation to an asymptomatic daughter and to a son with XLRP.
Although three different loci (RP3, RP2 and RP15) have been proposed on the short arm of the X-chromosome by linkage analysis, RP3 represents the disease locus in the majority of XLRP families.
The clinical phenotype was consistent with XLRP, supporting the observation that the mutations in the 3' end of the ORF15 coding sequence give rise to XLRP.
Identification of novel RPGR (retinitis pigmentosa GTPase regulator) mutations in a subset of X-linked retinitis pigmentosa families segregating with the RP3 locus.
Retinitis pigmentosa GTPase regulator (RPGR) gene sequence variants account for the vast majority of X linked retinitis pigmentosa (RP), which is one of the most severe forms of RP.
In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum.
The cilia-expressed gene RPGR (retinitis pigmentosa GTPase regulator) is mutated in patients with X-linked retinitis pigmentosa (XLRP) and encodes multiple protein isoforms with a common N-terminal domain homologous to regulator of chromosome condensation 1 (RCC1), a guanine nucleotide exchange factor (GEF) for Ran GTPase.
A total of 240 different RPGR mutations have been reported, including 24 novel ones in this work, which are associated with X-linked retinitis pigmentosa (XLRP) (95%), cone, cone-rod dystrophy, or atrophic macular atrophy (3%), and syndromal retinal dystrophies with ciliary dyskinesia and hearing loss (2%).
We tested whether CRISPR/Cas9 could be used in patient-specific iPSCs to precisely repair an RPGR point mutation that causes X-linked retinitis pigmentosa (XLRP).
The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease.
On the other hand, the female carriers of XLRP variants showed different RPGR-related consequences, ranging from rods hypofunctionality in c.1591G>T nonsense heterozygosity to no retinal changes in c.1105C>T polymorphic heterozygosity.