Osteogenesis Imperfecta Type VI in Individuals from Northern Canada

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• 作者：Leanne Ward ; Ghalib Bardai ; Pierre Moffatt…
• 刊名：Calcified Tissue International
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：98
• 期：6
• 页码：566-572
• 全文大小：1,281 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Endocrinology
  Orthopedics
  Cell Biology
  
• 出版者：Springer New York
• ISSN：1432-0827
• 卷排序：98

文摘

Osteogenesis imperfecta (OI) type VI is a recessively inherited form of OI that is caused by mutations in SERPINF1, the gene coding for pigment-epithelium derived factor (PEDF). Here, we report on two apparently unrelated children with OI type VI who had the same unusual homozygous variant in intron 6 of SERPINF1 (c.787-10C>G). This variant created a novel splice site that led to the in-frame addition of three amino acids to PEDF (p.Lys262_Ile263insLeuSerGln). Western blotting showed that skin fibroblasts with this mutation produced PEDF but failed to secrete it. Both children were treated with intravenous bisphosphonates, but the treatment of Individual 1 was switched to subcutaneous injections of denosumab (dose 1 mg per kg body weight, repeated every 3 months). An iliac bone sample obtained after 5 denosumab injections (and 3 months after the last injection) showed no change in the increased osteoid parameters that are typical of OI type VI, but the number of osteoclasts in trabecular bone was markedly increased. This suggests that the effect of denosumab on osteoclast suppression is of shorter duration in children with OI type VI than what has previously been reported on adults with osteoporosis.KeywordsChildrenFracturesOsteogenesis imperfectaPigment-epithelium derived factorSERPINF1