Is There Evidence For A Digenic Model In Stargardt Disease?

Abstract

Purpose: : Stargardt disease (STGD) is an autosomal recessive macular dystrophy caused by mutations in the ABCA4 gene. Screening of this gene in patients with a Stargardt phenotype often reveals only one mutation. We hypothesized that a second gene may play a role in the disease pathogenesis through a digenic mechanism, and considered the possible involvement of CNGB3, a gene causing achromatopsia.

Methods: : Patients (n=113) with a clinical diagnosis of Stargardt with at least one causative allele in ABCA4 as well asethnically matched controls (n=462) were screened for the c.1148delC common founder mutation in CNGB3 by sequence analysis.

Results: : Seven (3.2%) c.1148delC alleles were present in patients versus 9 (1.9%, P= 0.02) in controls, all in heterozygous state.

Conclusions: : The c.1148delC mutation in CNGB3 is relatively common in the Dutch population. STGD patients appear to carry this mutation more frequently than controls. Thus a digenic disease model may apply to STGD disease, and CNGB3 screening could have an additive value for STGD patients with a heterozygous ABCA4 mutation.

Keywords: retina • gene modifiers • genetics