title: Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1).
abstract: We have determined that two infants with perinatal lethal osteogenesis imperfecta in one family had the same new dominant point mutation. Although not detected in his dermal fibroblast DNA, the mutation was detected in somatic DNA from the father's hair root bulbs and lymphocytes. The mutation was also detected in the father's sperm, demonstrating that mosaicism in the father's germ line explains recurrence. The presence of both germ-line and somatic mosaicism indicates that the mutation occurred prior to segregation of the germ-line and somatic cell progenitors. About one in eight sperm carry the mutation, which implies that at least four progenitor cells populate the germ line in human males. The observation that the mosaic individual is clinically normal suggests that genetic diseases can have both qualitative and quantitative components.
authors.affiliation: Division of Medical Genetics, Cedars-Sinai Medical Center, Los Angeles.
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
authors.forename: B J
authors.initials: BJ
authors.lastname: Starman
authors.forename: B
authors.initials: B
authors.lastname: Blumberg
authors.forename: P H
authors.initials: PH
authors.lastname: Byers
mesh_terms: D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D015345:Oligonucleotide Probes; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy
chemical_list: D015345:Oligonucleotide Probes; D003094:Collagen; D004247:DNA