A novel CACNA1F gene mutation causes Aland Island eye disease.

PURPOSE Aland Island eye disease (AIED), also known as Forsius-Eriksson syndrome, is an X-linked recessive retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect, progressive myopia, and defective dark adaptation. Electroretinography reveals abnormalities in both photopic and scotopic functions. The gene locus for AIED has been mapped to the pericentromeric region of the X-chromosome, but the causative gene is unknown. The purpose of this study was to identify the mutated gene underlying the disease phenotype in the original AIED-affected family. METHODS All exons of the CACNA1F gene were studied by DNA sequencing. CACNA1F mRNA from cultured lymphoblasts was analyzed by RT-PCR and cDNA sequencing. RESULTS A novel deletion covering exon 30 and portions of flanking introns of the CACNA1F gene was identified in patients with AIED. Results from expression studies were consistent with the DNA studies and showed that mRNA lacked exon 30. The identified in-frame deletion mutation is predicted to cause a deletion of a transmembrane segment and an extracellular loop within repeat domain IV, and consequently an altered membrane topology of the encoded alpha1-subunit of the Ca(v)1.4 calcium channel. CONCLUSIONS Mutations in CACNA1F are known to cause the incomplete form of X-linked congenital stationary night blindness (CSNB2). Since the clinical picture of AIED is quite similar to CSNB2, it has long been discussed whether these disorders are allelic or form a single entity. The present study clearly indicates that AIED is also caused by a novel CACNA1F gene mutation.