Evaluation of the common variants of the ABCA4 gene in families with Stargardt disease and autosomal recessive retinitis pigmentosa

Stargardt disease (STGD) is one of the most common autosomal recessive retinal dystrophies with an estimated incidence of one in 10,000. It affects the central retina (macula). Retinitis pigmentosa (RP) comprises a large and exceptionally heterogeneous group of hereditary disorders of the retina. It is caused by the loss of photoreceptors. The condition is a degenerative disorder characterized by retinal pigment deposits and has an estimated incidence of one in 4,000. Although, to date, 45 known loci have been identified, none of them independently account for a substantial portion of RP. Recently, the photoreceptor cell-specific ATP-binding cassette transporter (ABCA4) gene was found to be mutated in patients with STGD as well as autosomal recessive RP. In order to further understand the contribution of this gene to the susceptibility to STGD and RP, we analyzed three unrelated STGD families and one autosomal recessive RP family specifically for the more common variants (A1038V, G1961E, 2588G↷C, R943Q or 2828G↷A) in the ABCA4 gene. Our analyses employing standard techniques such as polymerase chain reaction, restriction fragment length polymorphism, and direct DNA sequencing of amplified products were able to identify one common variant (R943Q) in all three STGD families but not in the RP family. All three affected STGD individuals, however, were heterozygous for this variation, and this alteration did not segregate with the disease and was also present in the normal controls. Similar analysis of other common variants revealed no pathogenic mutations in the STGD and RP families. It is likely that the variant identified in this study represents a rare polymorphism (non-pathogenic). Although, at present we cannot eliminate the possibility of this gene as a candidate gene, future extensive studies on this as well as other candidate genes may uncover the susceptibility gene for these recessive forms of the disorders in these families.