title: Genotype-phenotype correlation in Italian families with Stargardt disease.
abstract: Autosomal recessive Stargardt disease (STGD) has been associated with substantial genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD patients with complete genetic data (i.e. identified mutations on both alleles of the ABCA4 gene), we set out to determine phenotypic subtypes and to correlate these with specific ABCA4 alleles. Twenty-eight patients from 18 families with STGD/fundus flavimaculatus were investigated. All patients were submitted to complete ophthalmologic examination, electrophysiology, fluorescein angiography and ABCA4 gene chip analysis. Two main clinical phenotypes were observed among the examined patients. The severe phenotype was characterized by the onset of the disease <20 years and reduced ERG response, whereas the mild phenotype presented with later onset of the disease and a normal ERG response. Genetic analysis of the ABCA4 gene revealed, in the severe group, more frequently deletions, stop codons and insertions as compared to the mild phenotype group (p=0.0113 by Fisher's exact test). Moreover, the compound heterozygous mutations G1961E/5018+2T-->C found in 7 patients from 3 unrelated STGD families were associated with a mild phenotype in all subjects, except 1. This study documented variability of the clinical expression of STGD in relation to the age of onset of the disease, fundus appearance and the ERG response and allowed to subdivide patients into a severe and a mild phenotype group. These findings suggest that an extensive and comprehensive genetic analysis of STGD patients combined with thorough clinical evaluation, including the careful recording of the age of onset of the disease, would allow a more precise prognostic evaluation.
authors.affiliation: Department of Ophthalmology, Second University of Naples, Naples, Italy. franctes@tin.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Testa
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.forename: Anna
authors.initials: A
authors.lastname: Nesti
authors.forename: Settimio
authors.initials: S
authors.lastname: Rossi
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rinaldi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D004596:Electroretinography; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007558:Italy; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters