RGD Reference Report - CNGA3 mutations in hereditary cone photoreceptor disorders. - Rat Genome Database

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CNGA3 mutations in hereditary cone photoreceptor disorders.

Authors: Wissinger, B  Gamer, D  Jagle, H  Giorda, R  Marx, T  Mayer, S  Tippmann, S  Broghammer, M  Jurklies, B  Rosenberg, T  Jacobson, SG  Sener, EC  Tatlipinar, S  Hoyng, CB  Castellan, C  Bitoun, P  Andreasson, S  Rudolph, G  Kellner, U  Lorenz, B  Wolff, G  Verellen-Dumoulin, C  Schwartz, M  Cremers, FP  Apfelstedt-Sylla, E  Zrenner, E  Salati, R  Sharpe, LT  Kohl, S 
Citation: Wissinger B, etal., Am J Hum Genet 2001 Oct;69(4):722-37. Epub 2001 Aug 30.
RGD ID: 734792
Pubmed: PMID:11536077   (View Abstract at PubMed)
PMCID: PMC1226059   (View Article at PubMed Central)
DOI: DOI:10.1086/323613   (Journal Full-text)

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
color blindness  IAGP 734792 RGD 
color blindness  ISOCNGA3 (Homo sapiens)734792; 734792 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cnga3  (cyclic nucleotide gated channel subunit alpha 3)

Genes (Mus musculus)
Cnga3  (cyclic nucleotide gated channel alpha 3)

Genes (Homo sapiens)
CNGA3  (cyclic nucleotide gated channel subunit alpha 3)


Additional Information