Abstract
Purpose:
To present 4 novel mutations (3 frameshift and 1 missense) in the ABCA4 gene identified in brazilian patients with typical Stargardt disease type I.
Methods:
Ophthalmic examination was performed. Best corrected visual acuity (BCVA) was done with the Snellen chart. Retinography, (TRC50DX Topcon) and spectralis optical coherence tomography-OCT (Heidelberg Engineering Inc) were performed. Direct testing for mutations in the ABCA4 gene was performed by PCR amplification and bidirectional DNA sequencing of all coding exons and exon/intron boundaries in a CLIA certified laboratory. The results were analyzed and compared to the NCBI reference sequence NM_000350.2. The bioinformatic tools Polyphen-2 and Mutation Taster were used to predict the effect of the missense mutation on the protein.
Results:
BCVA range was from 20/100 to 20/800 in all patients. Retinography revealed typical macular beaten-bronze appearence, flecks in the younger patients, and dark choroid sign in all cases. The OCT showed a decreased foveal thickness on three patients. The ABCA4 sequencing identified the following novel mutations: homozygous c.2007G>C:p.M669I; heterozygous c.180_delG; heterozygous c.2782insG; and homozygous c.6471_delC. The novel missense mutation was predicted as disease causing by Polyphen-2 and Mutation Taster.
Conclusions:
Herein we’ve described 4 novel mutations in ABCA4 in brazilian patients with Stargardt disease, suggesting the existence of a different ABCA4 mutation prevalence in Brazil.
Keywords: 539 genetics •
696 retinal degenerations: hereditary •
702 retinitis