title: The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta.
abstract: Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen, and CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SP7 mutations were recently detected in a minority of patients with autosomal recessive OI. However, these findings have been mostly restricted to Western populations. The proportion of mutations and the correlations between genotype and phenotype in Chinese patients with OI are completely unknown. In this study, mutation analyses were performed for COL1A1, COL1A2, CRTAP, and LEPRE1 in a cohort of 58 unrelated Chinese patients with OI; the relationship between collagen type I mutations and clinical features was examined. A total of 56 heterozygous mutations were identified in COL1A1 and COL1A2, including 43 mutations in COL1A1 and 13 mutations in COL1A2. Among the 56 causative COL1A1 and COL1A2 mutations, 24 novel mutations were found, and 25 (44.6%) resulted in the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix. Compared with COL1A1 haploinsufficiency (n = 23), patients with mutations affecting glycine residues had a severe skeletal phenotype. In patients 18 years of age or older, on average patients with COL1A1 haploinsufficiency were taller and had higher femoral neck bone mineral density than with patients with helical mutations. Interestingly, we found two novel compound heterozygous mutations in the LEPRE1 gene in two unrelated families with autosomal recessive OI. Although the genotype-phenotype correlation is still unclear, our findings are useful to understand the genetic basis of Chinese patients with OI.
authors.affiliation: Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 600 Yi-Shan Rd, Shanghai 200233, People's Republic of China. ZZL2002@medmail.com.cn
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yao-hua
authors.initials: YH
authors.lastname: Ke
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Xiao
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Yu
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Gu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; 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; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics*; D064828:Prolyl Hydroxylases; D011509:Proteoglycans / Q000235:genetics*; D011859:Radiography; D055815:Young Adult
chemical_list: C108053:CRTAP protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011509:Proteoglycans; D064828:Prolyl Hydroxylases; C485657:P3H1 protein, human