A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants

Incomplete X-linked congenital stationary night blindness (CSNB) is a reces sive, non-progressive eye disorder characterized by abnormal electroretinog ram and psychophysical testing and can include impaired night vision, decre ased visual acuity, myopia, nystagmus, and strabismus. Including the 20 fam ilies previously reported (Bech-Hansen et al. 1998b), we have now analyzed patients from a total of 36 families with incomplete CSNB and identified 20 different mutations in the calcium channel gene CACNA1F. Three of the muta tions account for incomplete CSNB in two or more families, and a founder ef fect is clearly demonstrable for one of these mutations. Of the 20 mutation s identified, 14 (70%) are predicted to cause premature protein truncation and six (30%) to cause amino acid substitutions or deletions at conserved p ositions in the alpha (1F) protein. In characterizing transcripts of CACNA1 F we have identified several splice variants and defined a prototypical seq uence based on the location of mutations in splice variants and comparison with the mouse orthologue, Cacna1f.