Type V osteogenesis imperfecta: A new form of brittle bone disease
Type V osteogenesis imperfecta: A new form of brittle bone disease
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DOI：
10.1359/jbmr.2000.15.9.1650
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发表时间：
2000-09-01
影响因子：
6.2
通讯作者：
Bishop, NJ
中科院分区：
文献类型：
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作者：
Glorieux, FH;Rauch, F;Bishop, NJ
成骨不全症（OI）通常分为四种临床类型。其中，IV型成骨不全症明显代表了一组异质性疾病。这里我描述了7名成骨不全患者（3名女孩），她们通常被归类为成骨不全型TV，但可以与其他类型的TV患者区分开来。我们建议将这种疾病称为V型成骨不全，这些儿童有中重度长骨和椎体易碎性增加的病史，4例患者至少经历过一次增殖性骨痂形成，3例患者的家族史为成骨不全阳性，具有常染色体显性遗传模式。所有V型患者单侧或双侧前臂旋前/旋后活动范围受限，并伴有明显的骨间膜钙化。3例患者桡骨头前脱位，生长板附近有放射性致密的干骺带，腰椎骨密度低，与年龄匹配的IV型成骨不全患者相似，V型患者无蓝色巩膜或牙素体发育不全。但韧带松弛程度与IV型成骨不全患者相似。骨代谢生化指标水平总体在参考范围内，但在增生愈伤组织形成活跃期，血清碱性磷酸酶和尿I型胶原n端肽排泄明显增加。髂骨活检标本定性组织学显示片层排列不规则或呈网状。定量组织形态测量显示，与IV型成骨类似，皮质骨和松质骨数量减少。然而，与IV型成骨不同，V型成骨中反映松质骨重塑激活的参数大部分正常，而反映单个重塑部位骨形成过程的参数明显减少。对两种I型胶原基因的编码区和外显子/内含子边界进行突变筛选，未发现任何影响甘氨酸密码子或剪接位点的突变。总之，V型成骨不全是一种常染色体显性成骨不全的新形式，似乎与I型胶原蛋白突变无关。这种疾病背后的遗传缺陷仍有待阐明。
Osteogenesis imperfecta (OI) is commonly subdivided into four clinical types. Among these, OI type IV clearly represents a heterogeneous group of disorders. Here me describe 7 OI patients (3 girls), who would typically be classified as having OI type TV but who can be distinguished from other type TV 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.