Glorieux F H, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux D F, Fassier F, Bishop N J
Genetics Unit, Shriners Hospital, Montréal, Québec, Canada.
J Bone Miner Res. 2000 Sep;15(9):1650-8. doi: 10.1359/jbmr.2000.15.9.1650.
Osteogenesis imperfecta (OI) is commonly subdivided into four clinical types. Among these, OI type IV clearly represents a heterogeneous group of disorders. Here we describe 7 OI patients (3 girls), who would typically be classified as having OI type IV but who can be distinguished from other type IV patients. We propose to call this disease entity OI type V. These children had a history of moderate to severe increased fragility of long bones and vertebral bodies. Four patients had experienced at least one episode of hyperplastic callus formation. The family history was positive for OI in 3 patients, with an autosomal dominant pattern of inheritance. All type V patients had limitations in the range of pronation/supination in one or both forearms, associated with a radiologically apparent calcification of the interosseous membrane. Three patients had anterior dislocation of the radial head. A radiodense metaphyseal band immediately adjacent to the growth plate was a constant feature in growing patients. Lumbar spine bone mineral density was low and similar to age-matched patients with OI type IV. None of the type V patients presented blue sclerae or dentinogenesis imperfecta, but ligamentous laxity was similar to that in patients with OI type IV. Levels of biochemical markers of bone metabolism generally were within the reference range, but serum alkaline phosphatase and urinary collagen type I N-telopeptide excretion increased markedly during periods of active hyperplastic callus formation. Qualitative histology of iliac biopsy specimens showed that lamellae were arranged in an irregular fashion or had a meshlike appearance. Quantitative histomorphometry revealed decreased amounts of cortical and cancellous bone, like in OI type IV. However, in contrast to OI type IV, parameters that reflect remodeling activation on cancellous bone were mostly normal in OI type V, while parameters reflecting bone formation processes in individual remodeling sites were clearly decreased. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations affecting glycine codons or splice sites. In conclusion, OI type V is a new form of autosomal dominant OI, which does not appear to be associated with collagen type I mutations. The genetic defect underlying this disease remains to be elucidated.
成骨不全症（OI）通常分为四种临床类型。其中，IV型OI显然代表了一组异质性疾病。在此，我们描述了7例OI患者（3名女孩），他们通常会被归类为IV型OI，但可与其他IV型患者区分开来。我们建议将这种疾病实体称为V型OI。这些儿童有长骨和椎体中度至重度脆性增加的病史。4例患者至少经历过一次增生性骨痂形成。3例患者的家族史呈OI阳性，遗传模式为常染色体显性遗传。所有V型患者一侧或双侧前臂的旋前/旋后范围均受限，伴有骨间膜明显的放射学钙化。3例患者有桡骨头前脱位。在生长中的患者中，紧邻生长板的致密干骺端带是一个恒定特征。腰椎骨矿物质密度较低，与年龄匹配的IV型OI患者相似。V型患者均未出现蓝色巩膜或牙本质发育不全，但韧带松弛程度与IV型OI患者相似。骨代谢生化标志物水平一般在参考范围内，但在活跃的增生性骨痂形成期，血清碱性磷酸酶和尿I型胶原N-端肽排泄量显著增加。髂骨活检标本的定性组织学显示，骨板排列不规则或呈网状外观。定量组织形态计量学显示，皮质骨和松质骨量减少，与IV型OI相似。然而，与IV型OI不同的是，反映松质骨重塑激活的参数在V型OI中大多正常，而反映单个重塑部位骨形成过程的参数明显降低。对两个I型胶原基因的编码区和外显子/内含子边界进行突变筛查，未发现影响甘氨酸密码子或剪接位点的任何突变。总之，V型OI是常染色体显性OI的一种新形式，似乎与I型胶原突变无关。该疾病的遗传缺陷仍有待阐明。
