Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.
Crx is a novel paired-like homeodomain protein that is expressed predominantly in retinal photoreceptors and pinealocytes. Its gene has been mapped to chromosome 19q13.3, the site of a disease locus for autosomal dominant cone-rod dystrophy (CORDII). Analysis of the proband from a family with autosomal dominant CORD revealed an Arg41Trp substitution in the third residue of the CRX homeodomain. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. Recombinant CRX homeodomain containing the Arg41Trp substitution showed decreased DNA binding activity. Analysis of another 169 CORD probands identified three additional CRX sequence variations (Arg41Gln, Val242Met, and a 4 bp deletion in codons 196/7) that were not found among the controls. This data suggests that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function.
Swain
P K
PK
Department of Ophthalmology, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.
Chen
S
S
Wang
Q L
QL
Affatigato
L M
LM
Coats
C L
CL
Brady
K D
KD
Fishman
G A
GA
Jacobson
S G
SG
Swaroop
A
A
Stone
E
E
Sieving
P A
PA
Zack
D J
DJ
D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003062:Codon; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012160:Retina / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017384:Sequence Deletion; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014792:Visual Acuity
D003062:Codon; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein