Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta

Zhang,Hao; Yue,Hua; Wang,Chun; Hu,Weiwei; Gu,Jiemei; He,Jinwei; Fu,Wenzhen; Hu,Yunqiu; Li,Miao; Zhang,Zhenlin

doi:10.3892/mmr.2016.5835

Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta

Authors:
- Hao Zhang
- Hua Yue
- Chun Wang
- Weiwei Hu
- Jiemei Gu
- Jinwei He
- Wenzhen Fu
- Yunqiu Hu
- Miao Li
- Zhenlin Zhang
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Affiliations: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: October 12, 2016 https://doi.org/10.3892/mmr.2016.5835
Pages: 4918-4926

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Abstract

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by brittle bone fractures. The aim of the present study was to investigate the pathogenic gene mutation spectrum and clinical manifestations of mutations in collagen type I, alpha 1 (COL1A1) and collagen type I, alpha 2 (COL1A2) genes in Chinese patients with OI. A total of 61 unrelated Chinese OI patients with COL1A1 and COL1A2 mutations were recruited. All the exons and the exon-intron boundaries of the COL1A1 and COL1A2 genes were amplified and directly sequenced and lumbar spine bone mineral density was measured by dual‑energy X‑ray absorptiometry. The mutations of the 61 probands included 33 missense mutations, 8 nonsense mutations, 7 splicing variants and 13 frameshift mutations in COL1A1 and COL1A2 genes. A total of 25 novel mutations were identified, including 18 in COL1A1 and 7 in COL1A2. The mutations p.Gly257Arg, p.Gly767Ser and p.Gly821Ser in COL1A1 and p.Gly337Ser in COL1A2 may be located at a mutation hotspot for human OI due to the high repetition rate in OI patients. Family history was positive for OI in 33 probands (54%). All probands had suffered fractures and the most common fracture site was the femur. A total of 49 probands presented with blue sclerae (80.3%), 20 probands suffered from dentinogenesis imperfecta (32.8%) and 1 patient had hearing loss (1.6%). These findings may improve understanding of the pathogenic gene mutation spectrum and the clinical manifestations of mutations of COL1A1 and COL1A2 genes in Chinese patients with OI.

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1	Basel D and Steiner RD: Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition. Genet Med. 11:375–385. 2009. View Article : Google Scholar : PubMed/NCBI
2	Sillence DO and Rimoin DL: Classification of osteogenesis imperfect. Lancet. 1:1041–1042. 1978. View Article : Google Scholar : PubMed/NCBI
3	Rauch F and Glorieux FH: Osteogenesis imperfecta. Lancet. 363:1377–1385. 2004. View Article : Google Scholar : PubMed/NCBI
4	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
5	Van Dijk FS and Sillence DO: Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 164A:1470–1481. 2014. View Article : Google Scholar : PubMed/NCBI
6	Rauch F, Fahiminiya S, Majewski J, Carrot-Zhang J, Boudko S, Glorieux F, Mort JS, Bächinger HP and Moffatt P: Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB. Am J Hum Genet. 96:425–431. 2015. View Article : Google Scholar : PubMed/NCBI
7	Garbes L, Kim K, Rieß A, Hoyer-Kuhn H, Beleggia F, Bevot A, Kim MJ, Huh YH, Kweon HS, Savarirayan R, et al: Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta. Am J Hum Genet. 96:432–439. 2015. View Article : Google Scholar : PubMed/NCBI
8	Mendoza-Londono R, Fahiminiya S, Majewski J; Care4Rare Canada Consortium, ; Tétreault M, Nadaf J, Kannu P, Sochett E, Howard A, Stimec J, et al: Recessive osteogenesis imperfecta caused by missense mutations in SPARC. Am J Hum Genet. 96:979–985. 2015. View Article : Google Scholar : PubMed/NCBI
9	Cheung MS and Glorieux FH: Osteogenesis imperfecta: Update on presentation and management. Rev Endocr Metab Disord. 9:153–160. 2008. View Article : Google Scholar : PubMed/NCBI
10	Liu W, Gu F, Ji J, Lu D, Li X and Ma X: A novel COL1A1 nonsense mutation causing osteogenesis imperfecta in a Chinese family. Mol Vis. 13:360–365. 2007.PubMed/NCBI
11	Qin W, He JX, Shi J, Xing QH, Gao JJ and He L, Qian XQ, Liu ZJ, Shu AL and He L: Mutation detection of COL1A1 gene in a pedigree with osteogenesis imperfecta. Yi Chuan Xue Bao. 32:248–252. 2005.(In Chinese). PubMed/NCBI
12	Xia XY, Cui YX, Huang YF, Pan LJ, Yang B, Wang HY, Li XJ, Shi YC, Lu HY and Zhou YC: 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
13	Lu Y, Ren X, Wang Y, Li T, Li F, Wang S, Xu C, Wu G, Li H, Li G, et al: Mutational and structural characteristics of four novel heterozygous C-propeptide mutations in the proα1(I) collagen gene in Chinese osteogenesis imperfecta patients. Clin Endocrinol (Oxf). 80:524–531. 2014. View Article : Google Scholar : PubMed/NCBI
14	Zhang ZL, Zhang H, Ke YH, Yue H, Xiao WJ, Yu JB, Gu JM, Hu WW, Wang C, He JW and Fu WZ: The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. J Bone Miner Metab. 30:69–77. 2012. View Article : Google Scholar : PubMed/NCBI
15	Zhang Z, Li M, He JW, Fu WZ, Zhang CQ and Zhang ZL: Phenotype and genotype analysis of Chinese patients with osteogenesis imperfecta type V. PLoS One. 8:e723372013. View Article : Google Scholar : PubMed/NCBI
16	Zhang H, He JW, Gao G, Yue H, Yu JB, Hu WW, Gu JM, Hu YQ, Li M, Fu WZ, et al: Polymorphisms in the HOXD4 gene are not associated with peak bone mineral density in Chinese nuclear families. Acta Pharmacol Sin. 31:977–983. 2010. View Article : Google Scholar : PubMed/NCBI
17	Maynard LM, Guo SS, Chumlea WC, Roche AF, Wisemandle WA, Zeller CM, Towne B and Siervogel RM: Total-body and regional bone mineral content and areal bone mineral density in children aged 8–18 y: The Fels Longitudinal Study. Am J Clin Nutr. 68:1111–1117. 1998.PubMed/NCBI
18	Wang Y, Cui Y, Zhou X and Han J: Development of a high-throughput resequencing array for the detection of pathogenic mutations in osteogenesis imperfecta. PLoS One. 10:e01195532015. View Article : Google Scholar : PubMed/NCBI
19	Hoefele J, Mayer K, Marschall C, Alberer M, Klein HG and Kirschstein M: Rare co-occurrence of osteogenesis imperfecta type I and autosomal dominant polycystic kidney disease. World J Pediatr. April 8–2016.(Epub ahead of print). doi: 10.1007/s12519-016-0014-1. View Article : Google Scholar : PubMed/NCBI
20	Lin HY, Chuang CK, Su YN, Chen MR, Chiu HC, Niu DM and Lin SP: Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta. Orphanet J Rare Dis. 10:1522015. View Article : Google Scholar : PubMed/NCBI
21	Prockop DJ, Constantinou CD, Dombrowski KE, Hojima Y, Kadler KE, Kuivaniemi H, Tromp G and Vogel BE: Type I procollagen: The gene-protein system that harbors most of the mutations causing osteogenesis imperfecta and probably more common heritable disorders of connective tissue. Am J Med Genet. 34:60–67. 1989. View Article : Google Scholar : PubMed/NCBI
22	Rauch F, Lalic L, Roughley P and Glorieux FH: Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 18:642–647. 2010. View Article : Google Scholar : PubMed/NCBI
23	Byers PH: Brittle bones-fragile molecules: Disorders of collagen gene structure and expression. Trends Genet. 6:293–300. 1990. View Article : Google Scholar : PubMed/NCBI
24	Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Körkkö J, Prockop DJ, De Paepe A, 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 : PubMed/NCBI
25	Lee KS, Song HR, Cho TJ, Kim HJ, Lee TM, Jin HS, Park HY, Kang S, Jung SC and Koo SK: Mutational spectrum of type I collagen genes in Korean patients with osteogenesis imperfecta. Hum Mutat. 27:5992006. View Article : Google Scholar : PubMed/NCBI
26	Paterson CR, Monk EA and McAllion SJ: How common is hearing impairment in osteogenesis imperfecta? J Laryngol Otol. 115:280–282. 2001. View Article : Google Scholar : PubMed/NCBI
27	Kuurila K, Kaitila I, Johansson R and Grénman R: Hearing loss in Finnish adults with osteogenesis imperfecta: A nationwide survey. Ann Otol Rhinol Laryngol. 111:939–946. 2002. View Article : Google Scholar : PubMed/NCBI
28	Kuurila K, Grenman R, Johansson R and Kaitila I: Hearing loss in children with osteogenesis imperfecta. Eur J Pediatr. 159:515–519. 2000. View Article : Google Scholar : PubMed/NCBI
29	Ben Amor IM, Roughley P, Glorieux FH and Rauch F: Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res. 28:2001–2007. 2013. View Article : Google Scholar : PubMed/NCBI