+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

Journal of Genetics and Genomics 38(4): 149-156

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053657267

Download citation: RISBibTeXText

PMID: 21530898

DOI: 10.1016/j.jgg.2011.03.002

Related references

The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. Journal of Bone and Mineral Metabolism 30(1): 69-77, 2012

Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta. Molecular Medicine Reports 14(5): 4918-4926, 2016

Mutational analysis and prenatal diagnosis of COL1A1 and COL1A2 genes in four Chinese families affected with osteogenesis imperfecta. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 34(5): 705-708, 2018

Identification of type I collagen gene (COL1A2) mutations in nonlethal osteogenesis imperfecta. Human Molecular Genetics 2(8): 1319-1321, 1993

Characterization of point mutations in the collagen COL1A1 and COL1A2 genes causing lethal perinatal osteogenesis imperfecta. Journal of Biological Chemistry 264(27): 15809-15812, 1989

Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: Identification of common sequences of null-allele mutations. American Journal of Human Genetics 62(1): 98-110, 1998

Novel mutations in the SEC24D gene in Chinese families with autosomal recessive osteogenesis imperfecta. Osteoporosis International 28(4): 1473-1480, 2016

Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III. Acta Biochimica Polonica 65(1): 79-86, 2018

Recurrent mutations in the COL1A2 gene in patients with osteogenesis imperfecta. Clinical Genetics 59(5): 338-343, 2001

Novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta. International Journal of Molecular Medicine 41(6): 3662-3670, 2018

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV. Human Mutation 17(5): 434, 2001

Genotype-phenotype analysis of a rare type of osteogenesis imperfecta in four Chinese families with WNT1 mutations. Clinica Chimica Acta; International Journal of Clinical Chemistry 461: 172-180, 2017

Novel Mutations in the Wnt1, Tmem38b, P4hb, and Pls3 Genes in Four Unrelated Chinese Families with Osteogenesis Imperfecta. Endocrine Practice 25(3): 230-241, 2019

Osteogenesis imperfecta type III with intracranial hemorrhage and brachydactyly associated with mutations in exon 49 of COL1A2. American Journal of Medical Genetics. Part a 149a(3): 461-465, 2009

A novel DHPLC-based procedure for the analysis of COL1A1 and COL1A2 mutations in osteogenesis imperfecta. Journal of Molecular Diagnostics 13(6): 648-656, 2012