Mäkitie Outi, Susic Miki, Ward Leanne, Barclay Catherine, Glorieux Francis H, Cole William G
Division of Genetics and Genomic Biology, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet A. 2005 Sep 1;137A(3):241-8. doi: 10.1002/ajmg.a.30855.
The Schmid type of metaphyseal chondrodyplasia (MCDS) is characterized by short stature, widened growth plates, and bowing of the long bones. It results from autosomal dominant mutations of COL10A1, the gene which encodes alpha1(X) chains of type X collagen. We report the clinical and radiographic findings in 10 patients with MCDS and COL10A1 mutations. Six patients had lower limb deformities, which necessitated orthopedic surgeries in all of them. One patient demonstrated no deformities and normal stature at age 11 years (height -1.2 SDS) while the others manifested severe short stature (<-3.5 SDS). Radiographs showed metaphyseal changes which were most pronounced at the hips and knees. Five of the identified 10 mutations in COL10A1 were novel. Six mutations resulted in truncation of the NC1 domain while four mutations were single amino-acid substitutions. Our findings suggest that COL10A1 mutations result in a uniform pattern of growth plate abnormalities. However, the clinical variability in severity among affected individuals is greater than previously thought.
施密德型干骺端软骨发育不良（MCDS）的特征为身材矮小、生长板增宽以及长骨弯曲。它是由编码X型胶原蛋白α1(X)链的基因COL10A1的常染色体显性突变引起的。我们报告了10例患有MCDS和COL10A1突变患者的临床和影像学检查结果。6例患者存在下肢畸形，所有人都需要进行矫形手术。1例患者在11岁时无畸形且身材正常（身高标准差评分-1.2），而其他患者表现为严重身材矮小（<-3.5标准差评分）。X线片显示干骺端改变，在髋部和膝部最为明显。在已确定的COL10A1的10个突变中，有5个是新发现的。6个突变导致NC1结构域截短，4个突变是单氨基酸替换。我们的研究结果表明，COL10A1突变会导致生长板异常的统一模式。然而，受影响个体之间严重程度的临床变异性比之前认为的更大。
