title: Correlation of clinical and genetic findings in Hungarian patients with Stargardt disease.
abstract: OBJECTIVE
  Autosomal recessive Stargardt disease (arSTGD) presents with substantial clinical and genetic heterogeneity. This study was conducted to correlate foveolar thickness (FT) and total macular volume (TMV), measured by optical coherence tomography (OCT), with other clinical characteristics and with specific genetic variation in Hungarian patients with arSTGD.
  
  
  METHODS
  After a standard ophthalmic workup, both eyes of 35 patients with STGD from Hungary and of 25 age-matched healthy control subjects were tested with OCT. FT and TMV were measured automatically with the OCT mapping software in the nine Early Treatment Diabetic Retinopathy Study areas of 3500 microm in diameter. All patients were screened for mutations by a combination of the ABCR400 microarray and direct sequencing.
  
  
  RESULTS
  The patients with STGD presented with markedly thinned retina in the foveola and decreased macular volume, 72 microm and 1.69 mm3, respectively, compared with 169 microm and 2.48 mm3 in the normal subjects, respectively. Statistically significant correlation was observed between visual acuity (VA) and TMV and between VA and FT. Disease-associated mutations were detected in 23 (65.7%) of 35 patients, including 48.5% with both alleles and 17.2% with one allele. The most frequent ABCA4 alleles in Hungarian patients with STGD were L541P/A1038V (in 28% of all patients), G1961E (20%) and IVS40+5G-->A (17%). Specific genotypes correlated with some phenotypic features and allowed for predictions of the disease progression.
  
  
  CONCLUSIONS
  Hungarian patients with STGD presented with extensive foveolar thinning and macular volume loss. Genetic analysis detected several ABCA4 alleles at high frequency in the cohort of patients, suggesting founder effect(s). Unusually homogeneous distribution of disease-associated mutations aided genotype-phenotype correlation analyses in this population.
authors.affiliation: 2nd Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Hargitai
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.forename: Gabor M
authors.initials: GM
authors.lastname: Somfai
authors.forename: Rita
authors.initials: R
authors.lastname: Vamos
authors.forename: Agnes
authors.initials: A
authors.lastname: Farkas
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Salacz
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D005260:Female; D018703:Founder Effect; D005584:Fovea Centralis / Q000473:pathology*; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D006814:Hungary / Q000208:ethnology; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters