A novel GUCY2D mutation, V933A, causes central areolar choroidal dystrophy.
OBJECTIVE
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.
Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Royal Victoria Hospital, Belfast, UK. a.hughes@qub.ac.uk
Anne E
AE
Hughes
Weihua
W
Meng
Andrew J
AJ
Lotery
Declan T
DT
Bradley
D015862:Choroid Diseases / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D009660:Northern Ireland; D011956:Receptors, Cell Surface / Q000235:genetics*
D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase