title: Spondyloepiphyseal dysplasia and precocious osteoarthritis in a family with an Arg75-->Cys mutation in the procollagen type II gene (COL2A1).
abstract: Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious osteoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg-->Cys mutation in one allele. The proband is a member of a large Chilean kindred presenting with chondrodysplasia of the hips, knees, shoulders, elbows, and spine associated with severe, early-onset osteoarthritis. All affected individuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the mutation segregated with the disease with a lod score of 2.2 at zero recombination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second example of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilaginous disease and is the first example of a point mutation in the amino terminal region of the alpha 1(II) chain, that results in a spondyloepiphyseal dysplastic phenotype.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107.
authors.forename: C J
authors.initials: CJ
authors.lastname: Williams
authors.forename: E L
authors.initials: EL
authors.lastname: Considine
authors.forename: R G
authors.initials: RG
authors.lastname: Knowlton
authors.forename: A
authors.initials: A
authors.lastname: Reginato
authors.forename: G
authors.initials: G
authors.lastname: Neumann
authors.forename: D
authors.initials: D
authors.lastname: Harrison
authors.forename: P
authors.initials: P
authors.lastname: Buxton
authors.forename: S
authors.initials: S
authors.lastname: Jimenez
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D002648:Child; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000150:complications / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000235:genetics*
chemical_list: D017931:DNA Primers; D011347:Procollagen; D001120:Arginine; D003545:Cysteine