A Novel CACNA1F Gene Mutation in the Original Family With Åland Island Eye Disease

Abstract

Purpose: : Åland Island eye disease (AIED), also known as Forsius–Eriksson syndrome, is an X–chromosomal recessive retinal disease characterized by a combination of fundal hypopigmentation, decreased visual acuity due to foveal hypoplasia, nystagmus, astigmatism, progressive myopia and defective dark adaptation. AIED has been localized to the pericentromeric region of the X–chromosome, but the causative gene is still unknown. The purpose of this study was to identify the mutated gene underlying the disease phenotype in the original AIED family.

Methods: : All exons and flanking intronic regions of the CACNA1F gene were studied by direct PCR–based DNA sequencing. CACNA1F mRNA from cultured lymphoblasts was analyzed by RT–PCR and cDNA sequencing.

Results: : A novel deletion in the CACNA1F gene was identified, covering a single exon and portions of the flanking introns. Expression studies indicated that the particular exon was excluded from the mRNA. This CACNA1F mutation co–segregated completely with the disease phenotype in the AIED family and was not observed in 121 control chromosomes.

Conclusions: : Mutations in CACNA1F are known to cause the incomplete form of X–linked congenital stationary night blindness (CSNB2). It has long been discussed, whether AIED and CSNB2 are a single entity or allelic diseases. CACNA1F mutations have been identified in patients with an AIED–like phenotype, but previous studies failed to reveal any CACNA1F mutation in patients from the original AIED family. Our results now show that AIED is caused by a novel deletion mutation within CACNA1F.

Keywords: gene screening • mutations • retinal degenerations: hereditary