Walter Kerstin, Tansek Mojca, Tobias Edward S, Ikegawa Shiro, Coucke Paul, Hyland James, Mortier Geert, Iwaya Tsutomu, Nishimura Gen, Superti-Furga Andrea, Unger Sheila
Centre for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
Am J Med Genet A. 2007 Jan 15;143A(2):161-7. doi: 10.1002/ajmg.a.31516.
Skeletal dysplasias induced by mutations in the collagen 2 gene (the so-called "type 2 collagenopathies") form a wide spectrum in severity and are distinguished by subtle clinical and radiographic differential signs. The unifying features are predominant involvement of the vertebral bodies and the epiphyses of the long bones ("spondylo-epiphyseal" pattern). A mild degree of metaphyseal dysplasia can be seen in the so-called Strudwick variant of spondyloepimetaphyseal dysplasia and is generally mild or absent in other forms. We report here on four individuals with COL2A1 mutations associated with marked metaphyseal involvement with only mild epiphyseal and spondylar changes. One patient who carried a Gly283Arg substitution had a pattern of metaphyseal dysplasia that corresponded precisely to what was termed "Murdoch type metaphyseal dysplasia" in 1960s and was renamed Strudwick type SEMD in 1980s; the second patient carried a Gly181Arg substitution and had severe metaphyseal dysplasia with fractures at the metaphyses reminiscent of the "corner fractures" or Sutcliffe type spondylometaphyseal dysplasia. The third patient also had major metaphyseal involvement but more epiphyseal changes than the others in this study and had a Gly922Arg mutation in COL2A1. The final patient had a small in-frame deletion and unusually ballooned and distorted metaphyses. While it remains true that most individuals with COL2A1 mutations have chondrodysplasia with a spondylo-epiphyseal pattern, metaphyseal involvement is not incompatible with a COL2A1 dysplasia and mutation analysis can be indicated. The observation of these individuals with metaphyseal dysplasia indicates that the phenotypic spectrum associated with mutations in type 2 collagen, the main cartilage protein, is even wider than hitherto assumed.
由胶原蛋白2基因（所谓的“2型胶原病”）突变引起的骨骼发育不良在严重程度上呈现出广泛的谱系，并以细微的临床和影像学鉴别体征为特征。其共同特征是椎体和长骨骨骺（“脊椎骨骺”模式）的主要受累。在脊椎骨骺发育异常的所谓Strudwick变异型中可出现轻度的干骺端发育异常，而在其他形式中通常较轻或不存在。我们在此报告了4例与明显的干骺端受累相关的COL2A1突变个体，仅有轻度的骨骺和脊柱改变。一名携带Gly283Arg替代突变的患者具有的干骺端发育异常模式与20世纪60年代所称的“默多克型干骺端发育异常”完全一致，并在80年代重新命名为Strudwick型脊椎骨骺发育异常；第二名患者携带Gly181Arg替代突变，患有严重的干骺端发育异常，干骺端骨折让人联想到“角状骨折”或Sutcliffe型脊椎干骺端发育异常。第三名患者也有主要的干骺端受累，但在本研究中比其他患者有更多的骨骺改变，且COL2A1基因有Gly922Arg突变。最后一名患者有一个小的框内缺失，干骺端异常膨胀和变形。虽然大多数COL2A1突变个体确实患有脊椎骨骺模式的软骨发育异常，但干骺端受累与COL2A1发育异常并不矛盾，可进行突变分析。对这些有干骺端发育异常个体的观察表明，与主要软骨蛋白2型胶原蛋白突变相关的表型谱系比迄今所认为的还要广泛。
