van Dijk Fleur S, Cobben Jan M, Maugeri Alessandra, Nikkels Peter G J, van Rijn Rick R, Pals Gerard
VU medisch centrum, afd. Klinische Genetica, Amsterdam.
Ned Tijdschr Geneeskd. 2012;156(21):A4585.
Osteogenesis imperfecta is a hereditary connective tissue disorder characterized primarily by fractures with no or small causal antecedent; in most patients this is a consequence of diminished or abnormal production of collagen type I. It is a clinically heterogeneous disorder: it has been proposed recently to classify osteogenesis imperfecta in types I-V on the basis of the clinical picture and radiology. It is also a genetically heterogeneous disorder; 90% of cases are due to autosomal dominant mutations, while the remaining 10% are due to autosomal recessive mutations or of unknown cause. Osteogenesis imperfecta type I and to a lesser extent type IV are important differential diagnostic considerations in case of suspicion of non-accidental injury (NAI). When osteogenesis imperfecta is suspected, DNA analysis of the dominant COL1A1 and COL1A2 genes is currently the starting point for laboratory diagnosis unless there are strong indications for a recessive cause. Protein analysis based on skin biopsy remains indicated in specific cases.
成骨不全症是一种遗传性结缔组织疾病,主要特征为骨折,且无明显或仅有轻微的诱发因素;在大多数患者中,这是由于I型胶原蛋白生成减少或异常所致。它是一种临床异质性疾病:最近有人提议根据临床表现和放射学特征将成骨不全症分为I-V型。它也是一种基因异质性疾病;90%的病例是由常染色体显性突变引起的,其余10%是由常染色体隐性突变或原因不明引起的。在怀疑非意外伤害(NAI)的情况下,I型成骨不全症以及程度较轻的IV型成骨不全症是重要的鉴别诊断考虑因素。当怀疑有成骨不全症时,除非有强烈迹象表明是隐性病因,否则目前实验室诊断的起点是对显性的COL1A1和COL1A2基因进行DNA分析。在特定情况下,基于皮肤活检的蛋白质分析仍然是必要的。