Novel KCNV2 mutations in cone dystrophy with supernormal rod electroretinogram.
OBJECTIVE
To describe patients with cone dystrophy and supernormal rod electroretinogram (ERG) and search for mutations in the recently described KCNV2 gene.


METHODS
Clinical and molecular study.


METHODS
Patients from three families originating from France, Morocco, and Algeria had standard ophthalmologic examination and color vision analysis, Goldmann perimetry, International Society for Clinical Electrophysiology of Vision (ISCEV) protocol in accordance with ERG testing, autofluorescence evaluation, and optical coherence tomography 3 scanning. The two coding exons of KCNV2 were polymerase chain reaction amplified and sequenced.


RESULTS
All patients had the characteristic features of supernormal, delayed rod ERG responses at the highest levels of stimulation and markedly reduced cone responses. In the French family, two affected sisters were compound heterozygotes for the recurrent c.1381G>A (Gly461Arg) mutation and for a novel c.442G>T (Glu148Stop) mutation. In the Moroccan family, affected members were homozygotes for the novel c.1404delC mutation (His468fsX503) and in the Algerian family, the proband was homozygote for the novel c.1001delC mutation (Ala334fsX453). In the three families, parents were unaffected heterozygote carriers. None of the mutations were present in 50 control chromosomes.


CONCLUSIONS
The three novel truncative mutations are likely to be null mutations leading to loss of function, with no difference in the phenotype presentation. Amino acid changes are found exclusively in the N-terminal fragment of the protein and in the P-loop, indicating the importance of those regions for the function of the KCNV2 protein.
Ben Salah
Safouane
S
Genetics of Sensory Diseases and Department of Ophthalmology, Hospital of Montpellier, Montpellier, France.
Kamei
Satomi
S
Sénéćhal
Audrey
A
Lopez
Séverine
S
Bazalgette
Christian
C
Bazalgette
Cécile
C
Eliaou
Claudie Malrieu
CM
Zanlonghi
Xavier
X
Hamel
Christian P
CP
D000293:Adolescent; D000328:Adult; D002648:Child; D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D003241:Consanguinity; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010775:Photic Stimulation; D016133:Polymerase Chain Reaction; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D041623:Tomography, Optical Coherence
C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated