Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are dominantly inherited chondrodysplasias characterized by short stature and early-onset osteoarthrosis. The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. In three patients with these diseases, we identified COMP mutations in a region of the gene that encodes a Ca++ binding motif. Our data demonstrate that PSACH and some forms of MED are allelic and suggest an essential role for Ca++ binding in COMP structure and function.
Briggs
M D
MD
Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Cedars-Sinai Research Institute, Los Angeles, California 90048, USA.
Hoffman
S M
SM
King
L M
LM
Olsen
A S
AS
Mohrenweiser
H
H
Leroy
J G
JG
Mortier
G R
GR
Rimoin
D L
DL
Lachman
R S
RS
Gaines
E S
ES
D000130:Achondroplasia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics; D002356:Cartilage; D064236:Cartilage Oligomeric Matrix Protein; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004276:DNA, Satellite / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011859:Radiography; D012091:Repetitive Sequences, Nucleic Acid
D002147:Calmodulin; D064236:Cartilage Oligomeric Matrix Protein; D004276:DNA, Satellite; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D004815:Epidermal Growth Factor; D002118:Calcium