Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene.
OBJECTIVE
To investigate phenotypic variability in terms of best-corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations.


METHODS
Entire coding region analysis of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD seen in the Retina Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and visual fields.


RESULTS
All patients had heterozygous amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was found in a 30-year-old patient with severly affected vision. Two novel sequence changes were identified: a missense mutation in a mildly affected 44-year-old patient and a frameshift mutation in a severly affected 34-year-old patient.


CONCLUSIONS
The identified ABCA4 mutations were compatible with the resulting phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense mutations. Sequence changes, predicted to have more deleterious effect on protein function, resulted in a more severe phenotype. This case series of STGD patients demonstrates novel genotype/phenotype correlations, which may be useful to counselling of patients. This information may prove useful in selection of candidates for clinical trials in ABCA4 disease.
Southampton Eye Unit, Southampton General Hospital, Southampton, UK.
M
M
Gemenetzi
A J
AJ
Lotery
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D004594:Electrophysiology; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D000080362:Stargardt Disease; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters