Novel complex ABCA4 alleles in Brazilian patients with stargardt disease: Genotype-Phenotype Correlation

Mariana Vallim Salles, Fabiana Louise Motta, Elton Dias da Silva, Patricia Varela, Kárita Antunes Costa, Rafael Filippelli-Silva, Renan Paulo Martin, John Pei Wen Chiang, João Bosco Pesquero, Juliana Maria Ferraz Sallum

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


PURPOSE: To analyze the presence of complex alleles of the ABCA4 gene in Brazilian patients with Stargardt disease and to assess the correlation with clinical features. METHODS: This was an observational cross-sectional study. Patients with a diagnosis of Stargardt disease who presented three pathogenic variants of the ABCA4 gene or who had variants previously described as complex alleles were included. The relatives of these probands were evaluated in the segregation analysis. The patients were evaluated based on age at symptom onset and visual acuity, and the clinical characteristics were classified according to the findings observed on autofluorescence examination. RESULTS: Among the 47 families analyzed, approximately 30% (14/47) presented complex alleles. The segregation analysis in 14 families with cases of Stargardt disease identified three novel complex alleles and one previously described complex allele. The known complex allele p.[Leu541Pro; Ala1038Val] was identified in two families. The novel complex alleles identified were p.[Leu541Pro; Arg1443His] in five families, p.[Ser1642Arg; Val1682_Val1686del] in seven families, and p.[Pro1761Arg; Arg2106Cys] in one family. Furthermore, four new variants (p.Lys22Asn, p.Asp915Asn, p.Glu1447Val, and p.Pro1761Arg) were identified in the second allele of the ABCA4 gene. CONCLUSIONS: Segregation analysis is important in order to confirm the molecular diagnosis of patients with Stargardt disease, given the frequency of complex alleles in the ABCA4 gene. The various pathogenic variation combinations observed in this study were associated with different phenotypes.

Original languageEnglish (US)
Pages (from-to)5723-5730
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number13
StatePublished - Nov 2017


  • ABCA4 protein
  • Complex allele
  • Eye diseases
  • Hereditary
  • Human
  • Macular degeneration/genetics
  • Retinal dystrophy
  • Stargardt disease

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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