Schwabe Georg C, Türkmen Seval, Leschik Gundula, Palanduz Sukru, Stöver Brigitte, Goecke Timm O, Mundlos Stefan
Institut für Medizinische Genetik, Humboldt-Univeristät, Charité, Augustenburger Platz 1, 13353 Berlin, Germany.
Am J Med Genet A. 2004 Feb 1;124A(4):356-63. doi: 10.1002/ajmg.a.20349.
Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little finger with hyperphalangy, usually of the index and middle finger. Heterozygous mutations of the cartilage derived morphogenetic protein-1 (CDMP1) resulting in a loss of function have been reported in BDC. We here describe a large kindred with a semi-dominant form of BDC and pronounced ulnar deviation of the second and third digits. In this family a novel homozygous missense mutation was identified (517A > G) changing methionine to valine at amino acid position 173. The mutation is located within a highly conserved seven amino acid region of the prodomain of CDMP1. Hand radiographs of heterozygous mutation carriers showed mild shortening of the metacarpals IV and V; a finding confirmed by the analysis of their metacarpophalangeal profiles (MCPPs). The mutation described here points toward an important function of the prodomain for the folding, secretion, and availability of biologically active CDMP1.
C型短指症（BDC）的特征是示指、中指和小指的中节指骨缩短并伴有多指畸形，通常是示指和中指。已有报道称，软骨衍生形态发生蛋白-1（CDMP1）的杂合突变导致功能丧失与BDC有关。我们在此描述一个具有半显性形式BDC且第二和第三指明显尺侧偏斜的大家族。在这个家族中，鉴定出一种新的纯合错义突变（517A>G），该突变在氨基酸位置173处将甲硫氨酸变为缬氨酸。该突变位于CDMP1前结构域一个高度保守的七氨基酸区域内。杂合突变携带者的手部X线片显示第四和第五掌骨轻度缩短；这一发现通过对其掌指轮廓（MCPPs）的分析得到证实。此处描述的突变表明前结构域对于生物活性CDMP1的折叠、分泌和可用性具有重要作用。
