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

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.