title: Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia.
abstract: We have characterized a mutation in the type II collagen gene (COL2A1) that produces a form of spondyloepiphyseal dysplasia. The mutation is an internal tandem duplication of 45 base pairs within exon 48 and results in the addition of 15 amino acids to the triple-helical domain of the alpha 1 chains of type II collagen derived from the abnormal allele. Although the repeating (Gly-Xaa-Yaa)n motif that characterizes the triple-helical domain is preserved, type II collagen derived from cartilage of the affected individual contains a population with excessive posttranslational modification, consistent with a disruption in triple-helix structure. The mutation is not carried by either parent, indicating that the phenotype in the affected individual is due to a new dominant mutation. DNA sequence homology in the area of the duplication suggests that the mutation may have arisen by unequal crossover between related sequences, a proposed mechanism in the evolution and diversification of the collagen gene family.
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
authors.forename: G E
authors.initials: GE
authors.lastname: Tiller
authors.forename: D L
authors.initials: DL
authors.lastname: Rimoin
authors.forename: L W
authors.initials: LW
authors.lastname: Murray
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D015345:Oligonucleotide Probes; D010009:Osteochondrodysplasias / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D015345:Oligonucleotide Probes; D003094:Collagen; D004247:DNA