title: Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen.
abstract: Most individuals with osteogenesis imperfecta (OI) are heterozygous for dominant mutations in one of the genes that encode the chains of type I collagen. Each of the more than 30 mutations characterized to date has been unique to the affected member(s) of the family. We have determined that two individuals with a progressive deforming variety of OI, OI type III, have the same new dominant mutation [alpha 1(I)gly154 to arg] and that two unrelated infants with perinatal lethal OI, OI type II, share a second new dominant mutation [alpha 1(I)gly1003 to ser]. These mutations occurred at CpG dinucleotides, in a manner consistent with deamination of a methylated cytosine residue, and raise the possibility that CpG dinucleotides are common sites of recurrent mutations in collagen genes. Further, these findings confirm that the OI type-III phenotype, previously thought to be inherited in an autosomal recessive manner, can result from new dominant mutations in the COL1A1 gene of type-I collagen.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: C J
authors.initials: CJ
authors.lastname: Pruchno
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
authors.forename: G A
authors.initials: GA
authors.lastname: Wallis
authors.forename: M C
authors.initials: MC
authors.lastname: Willing
authors.forename: B J
authors.initials: BJ
authors.lastname: Starman
authors.forename: X M
authors.initials: XM
authors.lastname: Zhang
authors.forename: P H
authors.initials: PH
authors.lastname: Byers
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005804:Genes, Lethal; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*
chemical_list: D003094:Collagen; D004247:DNA; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide