title: Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.
abstract: Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or autosomal recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic examinations and identified at least one ABCA4 mutation in 18 patients (33%) with CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing revealed four novel missense mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG). Ophthalmoscopic abnormalities in CRD patients ranged from minor granular pigmentary changes in the posterior pole to widespread atrophy. In 12 patients with recordable electroretinogram (ERG) tracings, a cone-rod pattern was detected. Three patients demonstrated progression from a retinal dystrophy resembling STGD1 to a more widespread degeneration, and were subsequently diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients displayed ophthalmologic characteristics of classic RP. When detectable, ERG recordings in these patients demonstrated rod-cone patterns of photoreceptor degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip is an efficient first screening tool for arCRD.
authors.affiliation: Department of Ophthalmology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: Marijke
authors.initials: M
authors.lastname: Zonneveld
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maugeri
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012160:Retina / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters