Molecular scanning of the ABCA4 gene in Spanish patients with retinitis pigmentosa and Stargardt disease: identification of novel mutations

Eur J Ophthalmol. 2007 Sep-Oct;17(5):749-54. doi: 10.1177/112067210701700510.

Abstract

Purpose: Among the 500 ABCA4 mutations identified so far in the retina-specific ABC transporter (ABCA4) gene, only 20 have been described in patients with autosomal recessive retinitis pigmentosa (arRP). In this study the gene was screened for mutations in a cohort of 25 patients of Spanish origin, to further assess ABCA4 involvement in retinal dystrophies.

Methods: The 50 exons of the ABCA4 gene have been analyzed through denaturing high performance liquid chromatography (DHPLC) and direct sequencing of samples displaying altered elution profiles.

Results: Four new and five known mutations were identified in our patients; except for one new deletion detected in a patient with Stargardt disease, all the remaining variations are single nucleotide substitutions resulting in missense mutations.

Conclusions: The results further underline the genetic heterogeneity of retinal disorders, suggesting that more than one gene could differentially contribute to at least some forms of retinal degeneration. Finding a high proportion of novel mutations merits the use of scanning methodologies to analyze the whole coding region of the ABCA4 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • DNA / genetics*
  • Exons
  • Humans
  • Incidence
  • Macular Degeneration / epidemiology
  • Macular Degeneration / genetics*
  • Mutation*
  • Polymerase Chain Reaction
  • Retinitis Pigmentosa / epidemiology
  • Retinitis Pigmentosa / genetics*
  • Rod Cell Outer Segment
  • Spain / epidemiology

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • DNA