Dobbs Matthew B, Gurnett Christina A, Pierce Brandon, Exner G Ulrich, Robarge Jason, Morcuende Jose A, Cole William G, Templeton Peter A, Foster Bruce, Bowcock Anne M
Department of Orthopedic Surgery, Washington University School of Medicine, One Child Place, Suite 45 Saint Louis, Missouri 63110, USA.
J Orthop Res. 2006 Mar;24(3):448-53. doi: 10.1002/jor.20052.
Congenital vertical talus (CVT) is a primary dislocation of the talonavicular joint that often occurs in neuromusculoskeletal syndromes, but may also be seen as an isolated abnormality. Six families with isolated CVT were ascertained. DNA was isolated from 21 affected individuals and 17 unaffected individuals from these families, as well as from five sporadic patients with CVT. Variable expressivity was noted in three families, manifesting as clubfoot in three individuals. Genome-wide linkage analysis generated a maximum two-point logarithm of odds score on chromosome 2q with D2S1353 (Zmax = 1.43 at theta(max) = 0.1), 17 Mb from the HOXD gene cluster. DNA from one affected individual of each family was subjected to mutational analysis of the HOXD10 gene. A single missense mutation was identified (M319K, 956T > A) in the homeodomain recognition helix of the HOXD10 gene that segregated with disease in one large British family. This mutation was recently described in a family of Italian descent with CVT and Charcot-Marie-Tooth deformity HOXD10 gene mutations were not identified in any of the other families or sporadic patients with CVT, suggesting that genetic heterogeneity underlies this disorder.
先天性垂直距骨（CVT）是距舟关节的原发性脱位，常发生于神经肌肉骨骼综合征，但也可表现为孤立性异常。确定了6个患有孤立性CVT的家系。从这些家系的21名患病个体和17名未患病个体以及5名散发的CVT患者中提取了DNA。在3个家系中观察到可变表达，3名个体表现为马蹄内翻足。全基因组连锁分析在2号染色体上与D2S1353产生了最大两点对数优势分数（在θ(max)=0.1时Zmax = 1.43），距HOXD基因簇17 Mb。对每个家系的1名患病个体的DNA进行了HOXD10基因的突变分析。在一个英国家系中，在HOXD10基因的同源域识别螺旋中鉴定出一个单一错义突变（M319K，956T>A），该突变与疾病共分离。最近在一个患有CVT和夏科-马里-图思畸形的意大利裔家系中描述了这种突变。在任何其他家系或散发的CVT患者中均未鉴定出HOXD10基因突变，提示该疾病存在遗传异质性。
