Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta

Xu, Zhenping; Li, Yulei; Zhang, Xiangyang; Zeng, Fanming; Yuan, Mingxiong; Liu, Mugen; Wang, Qing Kenneth; Liu, Jingyu

doi:10.1016/j.jgg.2011.03.002

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…The most common mutations result in replacement of one single glycine in the many essential Gly-X-Y triplets in the triple helical region (p.179–1192). The substituted amino acid may include serine, arginine, aspartic acid, valine, or alanine at a single position ( Ben Amor et al , 2011 ; Xu et al , 2011 ). These point mutations that replace glycine can occur throughout most of the length of COL1A1 and affect collagen stability ( Witecka et al , 2008 ; Xu et al , 2008 ; Xiao et al , 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

et al. 2015

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Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients’ diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

et al. 2015

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“…16 In COL1A2 the variant p.(Tyr1117Cys) leads to OI type III but the published account does not suggest that there is increased bone density in the proband or in his elder siblings. 34 The p.(Asp1120Ala) variant in the same gene is described as resulting in increased bone density (unpublished).…”

Section: Helical-region Amino Acid Substitutionsmentioning

confidence: 99%

Osteogenesis Imperfecta Genotypes and Genotype–Phenotype Relationships

Dalgleish

2014

Osteogenesis Imperfecta

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“…That mineral nucleation begins inside collagen fibrils rather than on their surfaces calls for a robust chemical mechanism to ensure mineral ions are preferentially transported inside the fibrils rather than remaining in the vicinity of their surfaces, which the hydrophobic nature of collagen fibrils would tend to result in in the absence of a specific transport mechanism. Mutation of the final tyrosine residue in the α2 C-terminal telopeptide (in this work referred to as Y17) to cysteine has been found to correlate with cases of osteogenesis imperfecta (OI) (23), and several mutations and deletions of the key tyrosine and arginine residues in the α1 C-terminal telopeptide have also been proposed to correlate with OI (NIH ClinVar (24) accession codes: VCV000580848.5, VCV001486023.6, VCV001430512.4, VCV000456776.10, VCV001074867.6, VCV000930782.3, VCV000967962.6) further supporting the idea that these collagen C-terminal sequences are essential for functional bone calcification.…”

Section: Discussionmentioning

confidence: 96%

Poly(ADP-ribose) binding sites on collagen I fibrils for nucleating intrafibrillar bone mineral

Zecca,

Greer,

Duer

2024

Preprint

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Bone calcification is essential for vertebrate life. The mechanism by which mineral ions are transported into collagen fibrils to induce intrafibrillar mineral formation requires a calcium binding biopolymer that also has highly selective binding to the collagen fibril hole zones where intrafibrillar calcification begins, over other bone extracellular matrix components. Poly(ADP-ribose) has been shown to be a candidate biopolymer for this process and we show here that poly(ADP-ribose) has high affinity, highly conserved binding sites in the collagen type I C-terminal telopeptides. The discovery of these poly(ADP-ribose)-collagen binding sites gives new insights into the chemical mechanisms underlying bone calcification and possible mechanisms behind pathologies where there is dysfunctional bone calcification.

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Identification and molecular characterization of two novel mutations in COL1A2 in two Chinese families with osteogenesis imperfecta

Cited by 4 publications

References 34 publications

Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family

Osteogenesis Imperfecta Genotypes and Genotype–Phenotype Relationships

Poly(ADP-ribose) binding sites on collagen I fibrils for nucleating intrafibrillar bone mineral

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