Purchase this article with an account.
Anne E. Hughes, Weihua Meng, Andrew J. Lotery, Declan T. Bradley; A Novel GUCY2D Mutation, V933A, Causes Central Areolar Choroidal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2012;53(8):4748-4753. doi: 10.1167/iovs.12-10061.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To identify the genetic cause of central areolar choroidal dystrophy (CACD) in a large Northern Irish family.
We previously reported linkage of the locus for CACD in this family to an interval of approximately 5 cM on chromosome 17p13 flanked by polymorphic markers D17S1810 and CHLC GATA7B03. We undertook sequence capture, massively parallel sequencing and computational alignment, base-calling and annotation to identify a causative mutation. Conventional sequencing was used to confirm the results.
Deep sequencing identified a single-base substitution in guanylate cyclase 2D, membrane (retina-specific) gene (GUCY2D). The novel mutation segregated with the disease phenotype and resulted in substitution of valine by alanine at position 933, within the catalytic domain of the protein. It altered a motif that is strongly conserved in a large number of distantly related proteins across several species and was predicted to have a damaging effect on protein activity.
Mutations in GUCY2D have previously been associated with dominant cone–rod dystrophies (CORD6) and recessive forms of Leber's congenital amaurosis. This is the first report of a GUCY2D mutation causing CACD and adds to our understanding of genotype–phenotype correlation in this heterogeneous group of choroidoretinal dystrophies.
This PDF is available to Subscribers Only