Homozygous c.1937+1G>A splice-site variant of the ABCA4 gene is associated with Stargardt disease

Eur J Ophthalmol. 2014 Sep-Oct;24(5):814-7. doi: 10.5301/ejo.5000458. Epub 2014 Feb 24.

Abstract

Purpose: To report the phenotype of homozygous ABCA4 c.1937+1G>A splice-site variant associated with Stargardt disease.

Methods: Two siblings, a 10-year-old boy and a 32-year-old woman, born from consanguineous parents, presented with central vision loss and macular pigmentary atrophic changes suggestive of Stargardt disease. After genetic counselling, ABCA4 gene analysis was performed.

Results: The 2 siblings affected were shown to be homozygous for the c.1937+1G>A splice junction variant of the ABCA4 gene. Both parents were heterozygous for the same mutation; they were asymptomatic and the fundus examination revealed a normal appearance.

Conclusions: Thus far, ABCA4 c.1937+1G>A splice-site variant was shown to cause retinitis pigmentosa when in hemizygosity and Stargardt disease when present on one allele. In this family two sibs homozygous for the ABCA4 c.1937+1G>A splice-site variant have a less severe phenotype of Stargardt disease. This observation provides useful information for the diagnosis and counseling of patients with this ABCA4 variant.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Child
  • Consanguinity
  • DNA Mutational Analysis
  • Female
  • Homozygote
  • Humans
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics
  • Male
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein Isoforms / genetics
  • Siblings
  • Stargardt Disease
  • Tomography, Optical Coherence
  • Visual Acuity / physiology

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • Protein Isoforms