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The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta.
J Bone Miner Metab. 2012 Jan; 30(1):69-77.JB

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+Show Affiliations

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.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21667357

Citation

Zhang, Zhen-Lin, et al. "The Identification of Novel Mutations in COL1A1, COL1A2, and LEPRE1 Genes in Chinese Patients With Osteogenesis Imperfecta." Journal of Bone and Mineral Metabolism, vol. 30, no. 1, 2012, pp. 69-77.
Zhang ZL, Zhang H, Ke YH, et al. The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. J Bone Miner Metab. 2012;30(1):69-77.
Zhang, Z. L., Zhang, H., Ke, Y. H., Yue, H., Xiao, W. J., Yu, J. B., Gu, J. M., Hu, W. W., Wang, C., He, J. W., & Fu, W. Z. (2012). 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. https://doi.org/10.1007/s00774-011-0284-6
Zhang ZL, et al. The Identification of Novel Mutations in COL1A1, COL1A2, and LEPRE1 Genes in Chinese Patients With Osteogenesis Imperfecta. J Bone Miner Metab. 2012;30(1):69-77. PubMed PMID: 21667357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. AU - Zhang,Zhen-Lin, AU - Zhang,Hao, AU - Ke,Yao-hua, AU - Yue,Hua, AU - Xiao,Wen-Jin, AU - Yu,Jin-Bo, AU - Gu,Jie-Mei, AU - Hu,Wei-Wei, AU - Wang,Chun, AU - He,Jin-Wei, AU - Fu,Wen-Zhen, Y1 - 2011/06/14/ PY - 2010/12/24/received PY - 2011/05/16/accepted PY - 2011/6/14/entrez PY - 2011/6/15/pubmed PY - 2012/5/15/medline SP - 69 EP - 77 JF - Journal of bone and mineral metabolism JO - J Bone Miner Metab VL - 30 IS - 1 N2 - 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. SN - 1435-5604 UR - https://www.unboundmedicine.com/medline/citation/21667357/The_identification_of_novel_mutations_in_COL1A1_COL1A2_and_LEPRE1_genes_in_Chinese_patients_with_osteogenesis_imperfecta_ L2 - https://dx.doi.org/10.1007/s00774-011-0284-6 DB - PRIME DP - Unbound Medicine ER -