Characterising X-linked Inherited Retinal Disease in New Zealand identifies unique population demographics and genotypes.

Show simple item record Vincent, Andrea en Song, E en Kuruvilla, S en Raoof, N en Oliver, Verity en
dc.coverage.spatial Baltimore, MD, USA en 2018-10-09T23:03:07Z en 2017-05-09 en
dc.identifier.uri en
dc.description.abstract Purpose: To characterize the spectrum of X-linked inherited retinal dystrophy (XL-IRD), and to establish a genotype-phenotype correlation within the New Zealand population. Method: Probands with XL-IRD (Rod-cone dystrophy RP, Choroideraemia CHM, Congenital stationary night blindness CSNB, Retinoschisis RS, Blue cone monochromatism BCM, and Ocular albinism OA) were identified through family history and positive gene testing, from the 652 patients recruited in the IRD Database. Familial segregation and clinical data for affected male and obligate carrier female was undertaken. Bioinformatics of novel variants included pathogenicity prediction and frequency in population databases. Results: X-Linked inherited retinal disease was molecularly proven in 39 probands. (XLRP n=16, CHM n=6, CSNB n=5, XLRS n=8, BCM n=2, XLOA n=2), and segregation confirmed in family members where available. 37 unique pathogenic variants were present, with 17 not previously described (43.5%). Mutations in exon ORF15 of RPGR accounted for only 31% (5/16) of XLRP, with one novel change in a NZ Māori family, segregating with disease in 18 family members. One RP2 mutation was identified. Two reportedly unrelated Caucasian families had the same novel mutation (RPGR, intron3, c.248-10A>G). Novel RPGR variants were present in 2 Polynesian/NZ Māori families, the remainder were Caucasian. 4 families showed significant manifestations in female carriers, and were initially diagnosed with dominant disease. For CSNB, disease was attributable to CACNA1F in 4 families, with 75% variants novel. In CHM 83% of variants were novel, and 83% were indels. Conclusion: A knowledge of regional IRD genotypes and disease manifestation facilitates diagnosis for patients, in addition to using a targeted strategy for gene identification. In an era where clinical trials for some XL-IRD are already underway, a timely diagnosis is necessary. The spectrum of genotypes in an XL-IRD New Zealand population differs significantly that reported in other populations. The majority of variants identified were unique, with 43% of changes not previously reported. The frequency of ORF15 variants in XLRP was only 31%, suggesting screening RPGR prior to ORF15 is a more cost effective strategy. Significant disease manifestation in female carriers was observed, consistent with observation that XLRP may mimic autosomal dominant inheritance. This study highlights the importance of local knowledge in retinal diseases, to optimize diagnosis, management, and treatment. Lay person Ths study aimed to determine the underlying genetic mistakes causing X-linked Inherited Retinal Disease (IRD) within New Zealand. We collected clinical information and genetic test results, and established that nearly half of the gene changes causing disease in our popualtion, had never been described before, that nearly every family had their own unique gene change, and that many females in our population ( one third) were actually symptomatic with disease. This enables us to understand beeter this group of diseases in our population, and appropriately tailor gene testing en
dc.relation.ispartof Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) en
dc.relation.ispartofseries Investigative Ophthalmology & Visual Science en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Characterising X-linked Inherited Retinal Disease in New Zealand identifies unique population demographics and genotypes. en
dc.type Conference Poster en
dc.rights.holder Copyright: The authors en en
dc.rights.accessrights en
pubs.elements-id 697430 en Medical and Health Sciences en School of Medicine en Ophthalmology Department en
pubs.record-created-at-source-date 2017-10-19 en

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