These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Genotypic and phenotypic characterisation of RP2- and RPGR-associated X-linked inherited retinal dystrophy, including female manifestations.
    Author: Kuruvilla SE, Song E, Raoof N, van Bysterveldt K, Oliver VF, Hong SC, Al-Taie R, Wilson G, Vincent AL.
    Journal: Clin Exp Ophthalmol; 2023; 51(4):300-312. PubMed ID: 36882936.
    Abstract:
    BACKGROUND: With the promise of gene replacement therapy, eligible males and females with X-linked inherited retinal dystrophy (XL-IRD) should be identified. METHODS: Retrospective observational cohort study to establish the phenotypic and genotypic spectrum of XL-IRD within New Zealand (NZ). Thirty-two probands, including 9 females, with molecularly proven XL-IRD due to RP2 or RPGR mutations, and 72 family members, of which 43 were affected, were identified from the NZ IRD Database. Comprehensive ophthalmic phenotyping, familial cosegregation, genotyping, and bioinformatics were undertaken. Main outcome measures were: RP2 and RPGR pathogenic variant spectrum, phenotype in males and females (symptoms, age of onset, visual acuity, refraction, electrophysiology, autofluorescence, retinal appearance), and genotype-phenotype correlation. RESULTS: For 32 families, 26 unique pathogenic variants were identified; in RP2 (n = 6, 21.9% of all families), RPGR exons 1-14 (n = 10, 43.75%), and RPGR-ORF15 (n = 10, 34.3%). Three RP2 and 8 RPGR exons 1-14 variants are novel, rare, and cosegregate. Thirty-one percent of carrier females were significantly affected, with 18.5% of families initially classified as autosomal dominant. Of five Polynesian families, 80% had novel disease-causing variants. One Māori family showed keratoconus segregating with an ORF15 variant. CONCLUSIONS: Significant disease was present in 31% of genetically proven female carriers, often leading to an erroneous presumption of the inheritance pattern. Pathogenic variants in 44% of the families were in exon 1-14 of RPGR, more frequent than usually described, which may inform the gene testing algorithm. Proving cosegregation in families for novel variants and identifying affected females and males translates to optimised clinical care and potential for gene therapy.
    [Abstract] [Full Text] [Related] [New Search]