Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the alpha 1(I) gene (COL1A1) of type I collagen in a parent.

摘要: Fibroblasts from a man with mild form of osteogenesis imperfecta (OI) and his son perinatal lethal OI (OI type II) produced normal abnormal I procollagen molecules. The molecules synthesized by both cell strains contained one or two pro alpha 1(I) chains in which the glycine at position 550 triple-helical domain was substituted arginine as result G-to-A transition first base codon. Cells mother only By allele-specific oligonucleotide hybridization to amplified genomic sequences paternal tissues we determined that mutant allele accounted for approximately 50% COL1A1 alleles fibroblasts, 27% those blood, 37% sperm. These findings demonstrate father is mosaic potentially mutation suggest phenotype nature relative abundance different tissues. Furthermore, make it clear some individuals moderate forms are mutations will be their offspring.