Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F.
BACKGROUND
Incomplete X-linked congenital stationary night blindness (CSNB) is a clinically variable condition that has been shown to be caused by mutations in the calcium-channel CACNA1F gene. We assessed the clinical variability in the expression of the incomplete CSNB phenotype in a subgroup of patients of Mennonite ancestry with the same founder mutation.


METHODS
Sixty-six male patients from 15 families were identified with a common mutation in exon 27 of CACNA1F (L1056insC). Clinical variability in night blindness, reduced visual acuity, myopia, nystagmus and strabismus was examined.


RESULTS
At least one of the major features of CSNB (night blindness, myopia and nystagmus) was absent in 72% of the patients. All the examined features varied widely, both between and within families.


CONCLUSIONS
Although the patients shared a common CACNA1F mutation, there was considerable variability in the clinical expression of the incomplete CSNB phenotype. These findings suggest the presence of other genetic factors modifying the phenotype of this disorder.
Boycott
K M
KM
Department of Medical Genetics, Faculty of Medicine, University of Calgary, Alta.
Pearce
W G
WG
Bech-Hansen
N T
NT
D000293:Adolescent; D000328:Adult; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D005124:Eye Abnormalities / Q000235:genetics* / Q000503:physiopathology; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics / Q000503:physiopathology; D009755:Night Blindness / Q000235:genetics* / Q000503:physiopathology; D009759:Nystagmus, Pathologic / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014792:Visual Acuity; D014960:X Chromosome
C113330:CACNA1F protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type