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Oscar F. Chacon-Camacho, Juan C. Zenteno-Ruiz; First Report of Molecular Genetic Analysis of Stargardt Disease in Mexican Population. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1219.
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© ARVO (1962-2015); The Authors (2016-present)
Stargardt disease (STGD; OMIM # 248200) is an autosomal recessive retinal dystrophy occurring in 1 in 8,000-10,000 and recognized as the most common cause of inherited juvenile macular dystrophy. Typically initiates early in childhood or in adolescence with a fast, gradual and bilateral visual acuity decrease, central scotomas, discromatopsia, photophobia and development of yellow-orange flecks around the macula and/or midretinal periphery. It is caused by mutations on the ABCA4 gene localized on 1p13-p2. This gene is composed by 50 exons that encode a protein belonging to the ABC transporter family critical for photoreceptor metabolism. To date, more than 600 STGD-associated ABCA4 genetic variants has been reported worldwide. In this work, we describe the first molecular analysis of the ABCA4 gene on Mexican subjects with STGD.
Fourteen sporadic and 8 familial STGD cases of Mexican origin were included in the study. Probands underwent full ophthalmologic examination including fundus examination, FAG and ERG. Blood samples were obtained by venopuncture and genomic DNA was extracted. PCR amplification of the 50 exons and the intron-exon junctions of the ABCA4 gene was achieved using pairs of primers derived from the ABCA4 sequence. PCR products were purified and directly sequenced using the dideoxy chain terminators (BigDye) method. DNA from a total of 100 control individuals was analyzed to validate novel ABCA4 mutations.
Twenty out of 22 probands carried at least one ABCA4 mutation: 8 patients carried homozygous changes, 5 were compound heterozygotes and 7 carried heterozygous ABCA4 pathogenic mutation. Of 30 likely pathogenic sequence changes, 28 were missense mutations, including 6 novel, one novel frameshift mutation, and one novel nonsense mutation.
This study represents the first report of ABCA4 mutations in Latin American patients with Stargardt disease. A number of novel and previously reported ABCA4 mutations were recognized. Our results expand the mutational spectrum of STGD- related mutations by demonstrating 8 novel mutations in the ABCA4 gene.
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