A novel mild variant of osteogenesis imperfecta type I 
caused by a Gly1088Glu mutation in COL1A1

Xia,Xin‑Yi; Li,Wei‑Wei; Li,Na; Wu,Qiu‑Yue; Cui,Ying‑Xia; Li,Xiao‑Jun

doi:10.3892/mmr.2014.2084

June-2014 Volume 9 Issue 6

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June-2014 Volume 9 Issue 6

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Article

A novel mild variant of osteogenesis imperfecta type I caused by a Gly1088Glu mutation in COL1A1

Authors:
- Xin‑Yi Xia
- Wei‑Wei Li
- Na Li
- Qiu‑Yue Wu
- Ying‑Xia Cui
- Xiao‑Jun Li
View Affiliations / Copyright

Affiliations: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China
Pages: 2187-2190
|
Published online on: March 28, 2014

https://doi.org/10.3892/mmr.2014.2084
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Abstract

Osteogenesis imperfecta (OI), also known as brittle bone disease, characterized by multiplicative osteopsathyrosis, blue sclera, dentinogenesis imperfecta and mild audition, is a rare inherited connective tissue disease. There are seven types of OI, I to VII, among which type I‑IV are relatively common and associated with type I collagen. Defects in type I collagen synthesis or structure are responsible for the majority of clinical OI cases since collagen is the major matrix protein of all connective tissues. Type I collagen consists of two pro-α1 chains and one pro-α2 chain, which are encoded by two genes, COL1A1 and COL1A2, respectively. The two subunits have a Gly‑X‑Y repeat domain, of which glycine is highly conserved in the majority of species. Point mutations on these sites appear to trigger OI. In the current study, a heterozygous mutation, c.3263G>A, p.Gly1088Glu, was identified in the Gly‑X‑Y domain of type I collagen in an affected individual with type I OI. A lethal phenotype with the p.Gly1088Ala mutation was observed at the same site as the current findings. This suggests that variant characteristics of the substitution for Gly may trigger a varying degree of OI from lethal to mild, even when the mutation occurs at the same site. It is hypothesized that the study may provide insight into the phenotype‑genotype association and may assist, not only in the clinical diagnosis, but also in investigating the mechanism of collagen‑associated diseases.

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1	Byers PH: Disorders of collagen biosynthesis and structure. The Metabolic and Molecular Basis of Inherited Disease. Scriver CR, Beaudet AL, Sly WS and Valle D: 7th edition. McGraw-Hill; New York, NY: pp. 4029–4077. 1995
2	Byers PH, Wallis GA and Willing MC: Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet. 28:433–442. 1991. View Article : Google Scholar : PubMed/NCBI
3	Pollitt R, McMahon R, Nunn J, et al: Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I–IV. Hum Mutat. 27:7162006.
4	Morello R, Bertin TK, Chen Y, et al: CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell. 127:291–304. 2006. View Article : Google Scholar : PubMed/NCBI
5	Van Dijk FS, Nesbitt IM, Zwikstra EH, et al: PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet. 85:521–527. 2009.PubMed/NCBI
6	Marini JC, Forlino A, Cabral WA, et al: Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 28:209–221. 2007. View Article : Google Scholar
7	Xia XY, Cui YX, Huang YF, et al: A novel RNA-splicing mutation in COL1A1 gene causing osteogenesis imperfecta type I in a Chinese family. Clin Chim Acta. 398:148–151. 2008. View Article : Google Scholar : PubMed/NCBI
8	Körkkö J, Ala-Kokko L, De Paepe A, Nuytinck L, Earley J and Prockop DJ: 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. Am J Hum Genet. 62:98–110. 1998.
9	Lee KS, Song HR, Cho TJ, et al: Mutational spectrum of type I collagen genes in Korean patients with osteogenesis imperfecta. Hum Mutat. 27:5992006. View Article : Google Scholar : PubMed/NCBI
10	Forlino A, Cabral WA, Barnes AM and Marini JC: New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 7:540–557. 2011. View Article : Google Scholar : PubMed/NCBI
11	Boot-Handford RP and Tuckwell DS: Fibrillar collagen: the key to vertebrate evolution? A tale of molecular incest. Bioessays. 25:142–151. 2003. View Article : Google Scholar : PubMed/NCBI
12	Exposito JY, Cluzel C, Garrone R and Lethias C: Evolution of collagens. Anat Rec. 268:302–316. 2002. View Article : Google Scholar : PubMed/NCBI
13	Stover DA and Verrelli BC: Comparative vertebrate evolutionary analyses of type I collagen: potential of COL1a1 gene structure and intron variation for common bone-related diseases. Mol Biol Evol. 28:533–542. 2011. View Article : Google Scholar : PubMed/NCBI
14	Weng YC, Sonni A, Labelle-Dumais C, et al: COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol. 71:470–477. 2012. View Article : Google Scholar : PubMed/NCBI
15	Valli M, Sangalli A, Rossi A, et al: Osteogenesis imperfecta and type I collagen mutations A lethal variant carsed by a Gly910 - Ala substitution in the α1(I) chain. Eur J Biochem. 211:415–419. 1993.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A novel mild variant of osteogenesis imperfecta type I caused by a Gly1088Glu mutation in COL1A1

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