title: Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1.
abstract: We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the alpha 1(1)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964-1966 in exon 27 of COL1A1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in-frame deletion resulted in the removal of alanine-438 and Glu437Asp substitution in the pro alpha 1(I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Lund
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: F
authors.initials: F
authors.lastname: Skovby
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree
chemical_list: D003094:Collagen