Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Orphanet J Rare Dis. 2013 Sep 30;8:154. doi: 10.1186/1750-1172-8-154.
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous brittle bone disorder. Whereas dominant OI is mostly due to heterozygous mutations in either COL1A1 or COL1A2, encoding type I procollagen, recessive OI is caused by biallelic mutations in genes encoding proteins involved in type I procollagen processing or chaperoning. Hitherto, some OI cases remain molecularly unexplained. We detected a homozygous genomic deletion of CREB3L1 in a family with severe OI. CREB3L1 encodes OASIS, an endoplasmic reticulum-stress transducer that regulates type I procollagen expression during murine bone formation. This is the first report linking CREB3L1 to human recessive OI, thereby expanding the OI gene spectrum.
成骨不全症（OI）是一种临床表现和遗传异质性的脆骨病。显性 OI 主要是由于 COL1A1 或 COL1A2 中任一基因的杂合突变引起的，该基因编码 I 型前胶原，而隐性 OI 则是由于编码 I 型前胶原加工或伴侣蛋白的基因的双等位基因突变引起的。迄今为止，一些 OI 病例仍未得到分子解释。我们在一个严重 OI 的家系中检测到 CREB3L1 的纯合基因组缺失。CREB3L1 编码 OASIS，一种内质网应激传感器，在小鼠骨形成过程中调节 I 型前胶原的表达。这是首例将 CREB3L1 与人类隐性 OI 联系起来的报告，从而扩大了 OI 基因谱。
