A novel Gly to Arg substitution at position 388 of the alpha 1 chain of type I collagen in lethal form of osteogenesis imperfecta

作者：Galicka A^*; Wolczynski S; Lesniewicz R; Chyczewski L; Gindzienski A

来源：Acta Biochimica Polonica, 2002, 49(2): 443-450.

• collagen
• osteogenesis imperfecta

Cultured skin fibroblasts from a proband with a lethal form of osteogenesis imperfecta produce two forms of type I collagen chains, with normal and delayed electrophoretic migration; collagen of the proband's mother was normal. Peptide mapping experiments localized the structural defect in the proband to alpha1(I) CB8 peptide in which residues 123 to 402 are spaned. Direct sequencing of amplified cDNA covering this region revealed a G to A single base change in one allele of the alpha1(I) chain, that converted glycine 388 to arginine. Restriction enzyme digestion of the RT-PCR product was consistent with a heterozygous COL1A1 mutation. The novel mutation conforms to the linear gradient of clinical severity for the alpha1(I) chain and results in reduced thermal stability by 3degreesC and intracellular retention of abnormal molecules.

• 出版日期2002