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 Maori 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.
Subject(s)
Eye Proteins , GTP-Binding Proteins , Genetic Diseases, X-Linked , Membrane Proteins , Retinal Dystrophies , Retinitis Pigmentosa , Female , Humans , Male , DNA Mutational Analysis , Eye Proteins/genetics , Genetic Diseases, X-Linked/genetics , Genotype , GTP-Binding Proteins/genetics , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Mutation , Pedigree , Phenotype , Retinitis Pigmentosa/genetics , Retrospective Studies , New ZealandABSTRACT
BACKGROUND: Ocular myiasis though rare, is usually found in association with basal cell carcinoma. It is rarer still in tumors other than basal cell carcinoma. We report a case of ocular myiasis in a glioma which is hitherto unreported to the best of our knowledge. CASE: A 50 year old male presented with bleeding and maggots emanating from a tumourous outgrowth which had replaced his right eye. He complained of swelling and pain in his right eye for the last 2 years. Manual removal of maggots was carried out following which he underwent total excision of the mass and local debridement. Biopsy of the mass was consistent with astrocytoma. CONCLUSION: Myiasis though rare should be suspected in long standing neglected lesions with suggestive history. Infection, ischemic necrosis and malignancy coupled with overcrowding, poor living conditions, presence of excessive arthropods in the locality and low levels of hygiene drastically increase the risk of myiasis.