Mutational characterization of the P3H1/CRTAP/CypB complex in recessive osteogenesis imperfecta

• DOI: 10.4238/2015.december.1.36
• Publication Date: 2015-12-04T06:46:38Z
• Authors: C. Barbirato; M. Trancozo; M.G. Almeida; L.S. Almeida; T.O. Santos; J.C.G. Duarte; M.R.G.O. Rebouças; V. Sipolatti; V.R.R. Nunes; F. Paula
• Keywords: 0301 basic medicine; Extracellular Matrix Proteins; Membrane Glycoproteins; Genotype; DNA Mutational Analysis; Genes, Recessive; Exons; Osteogenesis Imperfecta; Collagen Type I; Introns; Prolyl Hydroxylases; Cyclophilins; 03 medical and health sciences; Gene Frequency; Multiprotein Complexes; Mutation; Humans; Proteoglycans; Protein Processing, Post-Translational; Alleles; Molecular Chaperones; Protein Binding

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone deformities and fractures.Most cases are caused autosomal dominant mutations in the type I collagen genes COL1A1 COL1A2; however, an increasing number of recessive other have been reported.The LEPRE1, CRTAP, PPIB encode proteins that form P3H1/CRTAP/CypB complex, which responsible for posttranslational modifications collagen.In general, these lead to severe lethal phenotypes OI.Here, we describe sixteen variations detected from 25 Brazilian patients with OI.Samples were screened on single-strand conformation polymorphism gels variants determined automated sequencing.Seven P3H1/CRTAP/CyPB osteogenesis ©FUNPEC-RP www.funpecrp.com.brGenetics Molecular Research 14 (4): 15848-15858 (2015) but absent control samples.LEPRE1 contained highest variants, including previously described West African allele (c.1080+1G>T) found one patient OI as well undescribed p.Trp675Leu change predicted be causing.In carried c.558A>G homozygous mutation, causing through alteration splice site.Genetic gene probably not pathogenic due their localization or because synonymous effect.This study enhances our knowledge about mutational pattern genes.In addition, results strengthen proposition LEPRE1 should first analyzed mutation detection studies OI.