Institute of Human Genetics, University Hospital, University of Munich, Munich, Germany.
BMC Med Genet. 2011 Nov 22;12:152. doi: 10.1186/1471-2350-12-152.
Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis.
The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures.
Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene.
Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.
FKBP10 基因突变首先在 III 型成骨不全症患者中被描述。两项后续研究发现 FKBP10 突变与 Bruck 综合征 1 型有关，后者是一种罕见的疾病，其特征为先天性挛缩和骨骼脆弱。这就提出了一个问题，即第一个报告中的患者是否确实患有单纯性成骨不全症，或者 Bruck 综合征是否是更好的诊断。
这里描述的患者患有严重的常染色体隐性成骨不全症，没有挛缩。
纯合子作图将 FKBP10 鉴定为候选基因，测序显示该基因中的一个碱基对交换导致 C 末端提前出现终止密码子。
我们的研究表明，FKBP10 突变不仅导致 Bruck 综合征或 III 型成骨不全症，还可导致具有产前发病的严重型孤立性 IV 型成骨不全症。此外，它将牙本质生成不全症添加到与 FKBP10 突变相关的临床症状谱中。
