Osteogenesis imperfecta type V: Genetic and clinical findings in eleven Chinese patients.
BACKGROUND
Osteogenesis imperfecta (OI) type V is a rare inherited disease characterized by multiple fractures, intraosseous membrane calcification, and hypercallus formation. We investigate the causative gene, phenotype and also observe the effects of zoledronic acid in Chinese OI type V patients.


METHODS
The clinical phenotype and causative gene mutation was investigated in eleven patients with type V OI. Patients were given a dose of zoledronic acid 5mg intravenously. Fracture incidence and Z-score of bone mineral density (BMD) were evaluated. Serum levels of biomarkers such as cross linked C-telopeptide of type I collagen (β-CTX) and safety parameters were assessed.


RESULTS
The c.-14C>T mutation in the 5' untranslated region of IFITM5 was detected in all patients. The phenotype was largely variable, and no significant correlation of genotype and phenotype was found. After one dose of zoledronic acid infusion, fracture incidence significantly dropped from 2fractures/year before treatment to 0fracture/year after treatment (P=0.01). Z score of lumbar spine BMD elevated from -2.6 to -1.3 (P<0.001). Serum β-CTX level decreased by 50% (P<0.05). No serious adverse event was found.


CONCLUSIONS
No obvious correlation was found between the genotype and phenotype. Zoledronic acid had significantly skeletal protective effects in OI of type V.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Yi
Y
Liu
BGI Shenzhen: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China; Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China.
Jiawei
J
Wang
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Doudou
D
Ma
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Fang
F
Lv
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Xiaojie
X
Xu
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Weibo
W
Xia
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Yan
Y
Jiang
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Ou
O
Wang
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Xiaoping
X
Xing
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Peiran
P
Zhou
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Jianyi
J
Wang
Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Wei
W
Yu
BGI Shenzhen: Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China; Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China. Electronic address: limeilzh@sina.com.
Mei
M
Li
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype
Mutation in IFITM5; OI type V; Osteogenesis imperfecta; Zoledronic acid