Clinical features of achromatopsia in Swedish patients with defined genotypes.
OBJECTIVE
To describe the clinical phenotype, with emphasis on the electrophysiological findings, of patients with autosomal recessive rod monochromacy (RM) and defined mutations in the CNGA3/CNGB3 genes.


METHODS
RM patients from eight different families were included in the study. Their genotypes were determined by DNA sequencing and/or RFLP analysis of PCR-amplified genomic segments of the CNGA3 and CNGB3 genes. For comparison, we investigated one patient with blue-cone monochromacy (BCM). The clinical examination included best-corrected visual acuity, fundus examination, and full-field ERG. In six patients, the examination was complemented by multifocal ERG (MERG).


RESULTS
Three patients had three different CNG3A genotypes. Five patients were homozygous and one patient compound heterozygous for a 1-bp deletion (1148delC) in the CNGB3 gene. All patients examined presented with a visual acuity of 0.1-0.15. Small residual cone responses were noted in four young RM patients. The oldest patient examined (age 47 years) presented with pigmentary changes in the mid-peripheral retina and concentric constrictions of the visual fields.


CONCLUSIONS
Patients with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the alpha- and beta-subunits of the cGMP-gated cation channel in cone photoreceptor function. Small remaining cone responses in a few of the younger patients and mid-peripheral pigmentary degenerations in the oldest patient examined indicate that there could be some degree of progression in retinal dysfunction in at least some patients with RM.
Eksandh
Louise
L
Department of Ophthalmology, University Hospital, Lund, Sweden. louise.eksandh@telia.com
Kohl
Susanne
S
Wissinger
Bernd
B
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics*; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010786:Photoreceptor Cells; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D013548:Sweden / Q000453:epidemiology
C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D006152:Cyclic GMP