Genetic and functional analyses of a novel mutation in CRTAP gene in osteogenesis imperfecta

Abstract

Background Autosomal recessive type of osteogenesis imperfecta (OI) is caused by mutation in the gene encoding the intracellular collagen-modifying complex: cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (LEPRE1) and cyclophilin B (PPIB). The complex is responsible for one step in collagen post-translational modification, the prolyl 3-hydroxylation of specific proline residues at position 986 of type I collagen chains. Method We identified the mutation and its effect on the qualitative and quantitative defects in type I collagen production by fibroblasts. A proband, 37-year-old female from a consanguineous family, without defects in type I collagen genes was analyzed the mutation in genes responsible for recessive type of OI: CRTAP, LEPRE1 and PPIB. Functional study was performed with Western blot, mass spectrophotometry and immunofluoresense microscopy. Result A novel homozygous mutation of CRTAP gene, c.1106 delA in exon 6, was identified. Its predicted protein was expected to premature stop codon 10 amino acid downstream. The affected CRTAP protein showed 37% decreased in 3-hydroxylation at α1 (I) Pro 986 compared with the wild type. With normal quantitative analysis and the expected deletion part located on the tail of the protein and decreased P3H1 protein in the ER on immunofluorescence microscopy. Conclusion These may correspond to its less severe in phenotype of our patient compared with those in recessive group.