Additional mutations of type X collagen confirm COL10A1 as the Schmid metaphyseal chondrodysplasia locus.
Type X collagen is a short chain collagen expressed in hypertrophic chondrocytes during bone growth. A 13bp deletion has been shown to segregate with Schmid metaphyseal chondrodysplasia, an autosomal dominant disorder of the osseous skeleton, in a large Mormon kindred. To increase our understanding of the role type X collagen plays in development we have used SSCP analysis to identify three additional mutations in patients with Schmid metaphyseal chondrodysplasia. Two are frameshift mutations (1856delC and 1992delCT) and one is a missense mutation (C591R). Of interest, the apparently unaffected mother of the patient with the missense mutation is a somatic mosaic for the mutant allele. All three mutations are in the carboxy-terminal non-collagenous domain suggesting that the effect of these mutations is to impair the mutant polypeptide's ability to participate in chain association and trimer formation.
McIntosh
I
I
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287.
Abbott
M H
MH
Warman
M L
ML
Olsen
B R
BR
Francomano
C A
CA
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003094:Collagen / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D016368:Frameshift Mutation; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
D003094:Collagen