CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.
Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
Kohl
Susanne
S
Molekulargenetisches Labor, Universitäts-Augenklinik Tübingen, Abt. Pathophysiologie des Sehens und Neuroophthalmologie, Germany. susanne.kohl@uni-tuebingen.de
Varsanyi
Balazs
B
Antunes
Gesine Abadin
GA
Baumann
Britta
B
Hoyng
Carel B
CB
Jägle
Herbert
H
Rosenberg
Thomas
T
Kellner
Ulrich
U
Lorenz
Birgit
B
Salati
Roberto
R
Jurklies
Bernhard
B
Farkas
Agnes
A
Andreasson
Sten
S
Weleber
Richard G
RG
Jacobson
Samuel G
SG
Rudolph
Günther
G
Castellan
Claudio
C
Dollfus
Helene
H
Legius
Eric
E
Anastasi
Mario
M
Bitoun
Pierre
P
Lev
Dorit
D
Sieving
Paul A
PA
Munier
Francis L
FL
Zrenner
Eberhart
E
Sharpe
Lindsay T
LT
Cremers
Frans P M
FP
Wissinger
Bernd
B
D000483:Alleles; D000818:Animals; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary; D054815:Cyclic Nucleotide-Gated Cation Channels; D004283:Dog Diseases / Q000235:genetics; D004285:Dogs; D005808:Genes, Recessive; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells
C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels