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A.C. Sodi, I. Passerini, F. Girolami, E. Pelo, U. Menchini, F. Torricelli; NOVEL MUTATIONS IN THE ABCR GENE ASSOCIATED WITH STARGARDT DISEASE IN ITALIAN PATIENTS . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2449.
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Purpose:Stargardt disease (STGD) is a progressive juvenile–to–young adult–onset macular degeneration, characterized by severe reduction of central visual acuity and normal peripheral vision. STGD is predominantly inherited as an autosomal recessive trait; even if autosomal dominant forms have been described. Homozygous and compound heterozygous mutations in the ABCR gene, encoding the photoreceptor–specific ATP–binding cassette (ABC) transporter, are responsible for recessive Stargardt macular dystrophy. In this study we determined the mutation spectrum in the ABCR gene in a group of Italian patients with autosomal recessive Stargardt disease . Methods: Thirteen families from central Italy , some members of which were affected by autosomal recessive Stargardt disease, were clinically examined. DNA samples were analyzed for mutations in all 50 exons of the ABCR gene by DHPLC approach ( with optimization of DHPLC conditions for mutation analysis ) and direct sequencing techniques. Results:All the affected subjects showed bilateral central vision loss with macular atrophy and yellow–white at the posterior pole, typical dark choroid in fluorescein angiography , normal electroretinogram , normal caliber of retinal vessels , no pigmented bone spicules in the retinal periphery. In all these patients we reported some mutations of ABCR gene . Some of them have been already described and among them Gly1961Glu was the most frequent in our series. Seven novel mutations were identified : 1) three missense mutations (Thr970Pro, Phe1015Ile and Leu2221Pro); 2) two nonsense mutations (Cys1177Stop and Trp1408Stop); 3) two small deletions (5905delG and 6636delA). The missense mutations were not detected in 150 unaffected control individuals (300 chromosomes) of Italian origin. Conclusions:Some novel mutations in ABCR gene in STGD patients were reported. These data confirm the extensive allelic heterogeneity of the ABCR gene, in agreement with previous observations in patients with Stargardt disease from Italy. The frequent report of novel mutations is probably related to the great number of exons in the ABCR gene, which favours rearrangements in DNA sequence.
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