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104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft 2006
Abstract
Abstract
FR.14.07 ABCA4 gene analysis in patients with cone and cone rod dystrophies Kitiratschky V.1, Schaich S.1, Zabel T.2, Zrenner E.2, Jägle H.2, Kohl S.1, Wissinger B.1
1Molekulargenetisches Labor, Universitäts-Augenklinik Tübingen, 2Abteilung für Pathophysiologie des Sehens und Neuro-Ophthalmologie, Universitäts-Augenklinik Tübingen Objective: Recent studies have shown that mutations in the ABCA4 gene may be the cause for autosomal recessive cone and cone rod dystrophies. This study examines the prevalence of ABCA4 gene mutations in a group of patients with familial autosomal recessive cone and cone rod dystrophies (CD/CRD).
Methods: Inclusion criteria to the study were a clinically diagnosed CD/CRD and presumable autosomal recessive inheritance with two or more affected family members. 70 independent families/patients fulfilled this criteria. Mutation analysis was performed using the ABCR400-Genechip (AsperOphthalmics, Tartu). The detected mutations were validated by means of additional DNA-Sequencing and segregation analysis in the families.
Results: Using genechip analysis for the ABCA4 gene in 26/70 (37%) patients presumable pathogenic mutations were detected. All mutations could be confirmed with DANN sequencing. In 12 patients (17%) mutations could be detected on both allels. 3 patients were homozygous, 9 patients were compound heterozygous for different ABCA4-mutations. In 6 cases a undependent and consistent segregation of the mutations could be demonstrated. In 14 patients only one mutated ABCA4 allel could be detectet using genechip analysis. 3 of these patients probably hat a complex allel, which is characterised as phase linkage of two co-segregating sequence variations. Such a phase linkage could be demonstrated with segregation analysis in 1 of 3 families. In one patient no mutation could be detected with genechip analysis but the proband was homozygous for all tested polymorphisms. Thus linkage with the ABCA4-Locus may be assumed. In ongoing sequence analyses patients with only one detected ABCA4 mutation will be further tested.
Conclusions: This study showed a high prevalence of ABCA4 gene mutations in patients with autosomal recessive CD/CRD. Through application of the Genechip in 1/3 of the patients at least one pathogenic mutation could be demonstrated. The results show a high specificity of genechip analysis but also suggest that the mutation spectrum in the ABCA4 gene is not yet fully represented.
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