Incomplete X-linked congenital stationary night blindness (CSNB) is a recessive, non-progressive eye disorder characterized by abnormal electroretinogram and psychophysical testing and can include impaired night vision, decreased visual acuity, myopia, nystagmus, and strabismus. Including the 20 families 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 mutations account for incomplete CSNB in two or more families, and a founder effect is clearly demonstrable for one of these mutations. Of the 20 mutations identified, 14 (70%) are predicted to cause premature protein truncation and six (30%) to cause amino acid substitutions or deletions at conserved positions in the α1F protein. In characterizing transcripts of CACNA1F we have identified several splice variants and defined a prototypical sequence based on the location of mutations in splice variants and comparison with the mouse orthologue, Canca1f.
Bibliographical noteFunding Information:
Acknowledgements This research was supported in part by the RP Research Foundation (Canada), the I.D. Bebensee Foundation, and an Alberta Oddfellow-Rebekah Visual Research Award. N.T.B.H. was supported by the Department of Ophthalmology (University of Alberta), The Alberta Children’s Hospital Foundation, and is the Roy Allen Investigator in Eyesight Research, Faculty of Medicine, University of Calgary. K.M.B. is the recipient of an Alberta Heritage Foundation for Medical Research Postdoctoral Fellowship. R.G.W. was supported by the Foundation Fighting Blindness and an unrestricted grant from Research to Prevent Blindness.