title: Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI, also known as brittle bone disease) is caused mostly by mutations in two type I collagen genes, COL1A1 and COL1A2 encoding the pro-α1 (I) and pro-α2 (I) chains of type I collagen, respectively. Two Chinese families with autosomal dominant OI were identified and characterized. Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1. Mutational analysis was carried out using direct DNA sequence analysis. Two novel missense mutations, c.3350A>G and c.3305G>C, were identified in exon 49 of COL1A2 in the two families, respectively. The c.3305G>C mutation resulted in substitution of a glycine residue (G) by an alanine residue (A) at codon 1102 (p.G1102A), which was found to be mutated into serine (S), argine (R), aspartic acid (D), or valine (V) in other families. The c.3350A>G variant may be a de novo mutation resulting in p.Y1117C. Both mutations co-segregated with OI in respective families, and were not found in 100 normal controls. The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans. Mutational analysis did not identify any mutation in the COX-2 gene (a modifier gene of OI). This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI, significantly expands the spectrum of COL1A2 mutations causing OI, and has a significant implication in prenatal diagnosis of OI.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Xu
authors.forename: Yulei
authors.initials: Y
authors.lastname: Li
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhang
authors.forename: Fanming
authors.initials: F
authors.lastname: Zeng
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Yuan
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Qing Kenneth
authors.initials: QK
authors.lastname: Wang
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D003094:Collagen / Q000737:chemistry / Q000235:genetics*; D024042:Collagen Type I; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011859:Radiography; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D003094:Collagen