title: Identification of the molecular defect in a family with spondyloepiphyseal dysplasia.
abstract: Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of inherited disorders characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. Evidence has suggested that SED may result from structural defects in type II collagen. To confirm the validity of this hypothesis, the structure of the "candidate" type II collagen gene (COL2A1) has been directly examined in a relatively large SED family. Coarse scanning of the gene by Southern blot hybridization identified an abnormal restriction pattern in one of the affected members of the kindred. Analysis of selected genomic fragments, amplified by the polymerase chain reaction, precisely localized the molecular defect and demonstrated that all affected family members carried the same heterozygous single-exon deletion. As a consequence of the mutation, nearly 90 percent of the assembled type II collagen homotrimers are expected to contain one or more procollagen subunits harboring an interstitial deletion of 36 amino acids in the triple helical domain.
authors.affiliation: Department of Microbiology and Immunology, State University of New York Health Science Center, Brooklyn 11203.
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Vissing
authors.forename: F
authors.initials: F
authors.lastname: Ramirez
authors.forename: D
authors.initials: D
authors.lastname: Rogers
authors.forename: D
authors.initials: D
authors.lastname: Rimoin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D002872:Chromosome Deletion; D003094:Collagen / Q000235:genetics*; D004262:DNA Restriction Enzymes; D004259:DNA-Directed DNA Polymerase; D005091:Exons; D005260:Female; D005784:Gene Amplification; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D011347:Procollagen / Q000235:genetics
chemical_list: D046911:Macromolecular Substances; D011347:Procollagen; D003094:Collagen; D004259:DNA-Directed DNA Polymerase; D004262:DNA Restriction Enzymes