title: [Screening and analysis of a new mutation of COL1A1 gene in a family with osteogenesis imperfecta].
abstract: OBJECTIVE
  To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta (OI).
  
  
  METHODS
  The family history of an OI pedigree, along with clinical data, was collected. Blood samples from the proband and his families, as well as 50 normal controls, were collected. Mutation of COL1A1 gene was screened using PCR-high resolution melting (PCR-HRM) and validated by sequencing.
  
  
  RESULTS
  PCR HRM method showed an abnormal result in proband COL1A133_34 exons, which Tm was 87.7℃, in contrast to the normal control (wt) Tm of 87.9±0.06℃. There was a significant difference between the proband and the normal control with the standardization curve and the difference curves. DNA sequencing showed that Y9COL1A1 gene exons 33_34 has lost a C base (c.2321delC), which resulted in a frameshift mutation and caused an premature termination codon (UAA) at amino acid 334, i.e., p.Pro774LeufsX334 The father and grandfather of the proband, both suffered from OI, were verified to be heterozygous for the same mutation. The same mutation was not found in 50 normal controls. Database search confirmed this to be a novel mutation. Pedigree analysis suggested that it has an autosomal dominant inheritance. The proband and patients from the family were clinically diagnosed as OI type I.
  
  
  CONCLUSIONS
  The study has identified a novel mutation of COL1A1 gene, c.2321delC. This frameshift mutation has caused a premature stop codon and reduced collagen type synthesis, characterized by a lighter OI clinical phenotype.
authors.affiliation: Department of Medical Laboratory, Tianjin Hospital, Tianjin 300211, P. R. China. Email: lig@tijmu.edu.cn.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Keqiu
authors.initials: K
authors.lastname: Li
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Ren
authors.forename: Xiaobo
authors.initials: X
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Shizhen
authors.initials: S
authors.lastname: Guan
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Jing
authors.forename: Guang
authors.initials: G
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010375:Pedigree
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain