Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.
Genes associated with inherited retinal degeneration have been found to encode proteins required for phototransduction, metabolism, or structural support of photoreceptors. Here we show that mutations in a novel photoreceptor-specific homeodomain transcription factor gene (CRX) cause an autosomal dominant form of cone-rod dystrophy (adCRD) at the CORD2 locus on chromosome 19q13. In affected members of a CORD2-linked family, the highly conserved glutamic acid at the first position of the recognition helix is replaced by alanine (E80A). In another CRD family, a 1 bp deletion (E168 [delta1 bp]) within a novel sequence, the WSP motif, predicts truncation of the C-terminal 132 residues of CRX. Mutations in the CRX gene cause adCRD either by haploinsufficiency or by a dominant negative effect and demonstrate that CRX is essential for the maintenance of mammalian photoreceptors.
Freund
C L
CL
Department of Genetics, The Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Gregory-Evans
C Y
CY
Furukawa
T
T
Papaioannou
M
M
Looser
J
J
Ploder
L
L
Bellingham
J
J
Ng
D
D
Herbrick
J A
JA
Duncan
A
A
Scherer
S W
SW
Tsui
L C
LC
Loutradis-Anagnostou
A
A
Jacobson
S G
SG
Cepko
C L
CL
Bhattacharya
S S
SS
McInnes
R R
RR
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010375:Pedigree; D010786:Photoreceptor Cells / Q000502:physiology; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000737:chemistry; D012162:Retinal Degeneration / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein