Original Article

Journal of Bone and Mineral Metabolism

, Volume 30, Issue 1, pp 69-77

First online:

The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta

  • Zhen-Lin ZhangAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Email author 
  • , Hao ZhangAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Yao-hua KeAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Hua YueAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Wen-Jin XiaoAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Jin-Bo YuAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Jie-Mei GuAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Wei-Wei HuAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • , Chun WangAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
    • , Jin-Wei HeAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
    • , Wen-Zhen FuAffiliated withMetabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai

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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.

Keywords

Osteogenesis imperfecta Collagen type I LEPRE1 Mutation