dc.contributor.author |
Vincent, Andrea |
en |
dc.contributor.author |
Abeysekera, Nandoun |
en |
dc.contributor.author |
van Bysterveldt, Katherine A |
en |
dc.contributor.author |
Oliver, Verity |
en |
dc.contributor.author |
Ellingford, Jamie M |
en |
dc.contributor.author |
Barton, Stephanie |
en |
dc.contributor.author |
Black, Graeme Cm |
en |
dc.date.accessioned |
2018-10-16T21:19:16Z |
en |
dc.date.issued |
2017-12 |
en |
dc.identifier.issn |
1442-6404 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/42070 |
en |
dc.description.abstract |
IMPORTANCE:This study identifies unique genetic variation observed in a cohort of Māori and Polynesian patients with rod-cone retinal dystrophies using a targeted next-generation sequencing retinal disease gene panel. BACKGROUND:With over 250 retinal disease genes identified, genetic diagnosis is still only possible in 60-70% of individuals and even less within unique ethnic groups. DESIGN:Prospective genetic testing in patients with rod-cone retinal dystrophies identified from the New Zealand Inherited Retinal Disease Database, PARTICIPANTS: Sixteen patients of Māori and Polynesian ancestry. METHODS:Next-generation sequencing of a targeted retinal gene panel. Sanger sequencing for a novel PDE6B mutation in subsequent Māori patients. MAIN OUTCOME MEASURES:Genetic diagnosis, genotype-phenotype correlation. RESULTS:Thirteen unique pathogenic variants were identified in 9 of 16 (56.25%) patients in 10 different genes. A definitive genetic diagnosis was made in 7/16 patients (43.7%). Six changes were novel and not in public databases of human variation. In four patients, a homozygous, novel pathogenic variant (c.2197G > C, p.(Ala 733Pro)) in PDE6B was identified and also present in a further five similarly affected Māori patients. CONCLUSIONS AND RELEVANCE:Over half of the Māori and Polynesian patients with inherited rod-cone diseases have no pathogenic variant(s) detected with a targeted retinal next-generation sequencing strategy, which is supportive of novel genetic mechanisms in this population. A novel PDE6B founder variant is likely to account for 16% of recessive inherited retinal dystrophy in Māori. Careful characterization of the clinical presentation permits identification of further Māori patients with a similar phenotype and simplifies the diagnostic algorithm. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Clinical & experimental ophthalmology |
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 |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Humans |
en |
dc.subject |
Retinitis Pigmentosa |
en |
dc.subject |
DNA |
en |
dc.subject |
Follow-Up Studies |
en |
dc.subject |
Prospective Studies |
en |
dc.subject |
Pedigree |
en |
dc.subject |
DNA Mutational Analysis |
en |
dc.subject |
Phenotype |
en |
dc.subject |
Mutation |
en |
dc.subject |
Adult |
en |
dc.subject |
Aged |
en |
dc.subject |
Middle Aged |
en |
dc.subject |
New Zealand |
en |
dc.subject |
Polynesia |
en |
dc.subject |
Female |
en |
dc.subject |
Male |
en |
dc.subject |
Cyclic Nucleotide Phosphodiesterases, Type 6 |
en |
dc.subject |
Genetic Variation |
en |
dc.subject |
Young Adult |
en |
dc.subject |
Genetic Testing |
en |
dc.subject |
Retinal Dystrophies |
en |
dc.title |
Next-generation sequencing targeted disease panel in rod-cone retinal dystrophies in Māori and Polynesian reveals novel changes and a common founder mutation. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1111/ceo.12983 |
en |
pubs.issue |
9 |
en |
pubs.begin-page |
901 |
en |
pubs.volume |
45 |
en |
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.pmid |
28488341 |
en |
pubs.end-page |
910 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Multicenter Study |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
625570 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Ophthalmology Department |
en |
dc.identifier.eissn |
1442-9071 |
en |
pubs.record-created-at-source-date |
2017-05-11 |
en |
pubs.dimensions-id |
28488341 |
en |