A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy

Anne E. Hughes, Weihua Meng, Andrew J. Lotery, Declan T. Bradley

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    Abstract

    PURPOSE. To identify the genetic cause of central areolar choroidal dystrophy (CACD) in a large Northern Irish family.

    METHODS. 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.

    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.

    CONCLUSIONS. 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. (Invest Ophthalmol Vis Sci. 2012; 53:4748-4753) DOI: 10.1167/iovs.12-10061

    Original languageEnglish
    Pages (from-to)4748-4753
    Number of pages6
    JournalInvestigative Ophthalmology & Visual Science
    Volume53
    Issue number8
    DOIs
    Publication statusPublished - Jul 2012

    Keywords

    • DEGENERATION
    • GENE
    • MISSENSE MUTATIONS
    • AUTOSOMAL-DOMINANT CONE
    • LOCALIZATION
    • RETINAL GUANYLATE-CYCLASE
    • ROD DYSTROPHY
    • LEBER CONGENITAL AMAUROSIS
    • CHROMOSOME 17P
    • RETGC1

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