Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the αI(I) gene (COLIAI) of type I collagen in a parent

• Published in: American journal of human genetics Vol. 46; no. 6; pp. 1034 - 1040
• Main Authors: WALLIS, G. A, STARMAN, B. J, ZINN, A. B, BYERS, P. H
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 1990
• Subjects: Biological and medical sciences; collagen I; Diseases of the osteoarticular system; genes; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; mosaicism; point mutation; Human; Molecular hybridization; Family study; Diseases of the osteoarticular system; Somatic cell; Genetic disease; Allele; Phenotype; Collagen; Osteogenesis imperfecta; Genetics; Mosaicism; Mutation; Molecular biology; Osteochondrodysplasia
• ISSN: 0002-9297; 1537-6605

Fibroblasts from a man with a mild form of osteogenesis imperfecta (OI) and from his son with perinatal lethal OI (OI type II) produced normal and abnormal type I procollagen molecules. The abnormal molecules synthesized by both cell strains contained one or two pro alpha 1(I) chains in which the glycine at position 550 of the triple-helical domain was substituted by arginine as the result of a G-to-A transition in the first base of the glycine codon. Cells from the mother produced only normal type I procollagen molecules. By allele-specific oligonucleotide hybridization to amplified genomic sequences from paternal tissues the authors determined that the mutant allele accounted for approximately 50% of the COL1A1 alleles in fibroblasts, 27% of those in blood, and 37% of those in sperm.