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先天性并指 (syndactyly)是一种以手脚发育异常为主要症状的常染色体显性遗传性疾病。临床症状主要为手指间由蹼相连。其中Ⅰ、Ⅱ、Ⅲ型先天性并指分别定位于 2q34～ 36、2q31～q32和 6q2 1～ 2 3 2。并指多指 (synpoly dactyly ;SPD)为Ⅱ型并指 (syndactyly ,typeⅡ ) ,通常情况下多为第 3、4手指和第 4、5脚趾受累 ,两指 (趾 )间由蹼相连接 ,不能分离。目前认为本病致病基因为HOXD13,定位于 2q31～q32。HOXD13位于HOXD基因簇中。HOXD基因簇中的 9个同源基因 (HOXD1, D3, D4 , D8, D9, D10 , D11, D12 , D13)根据其距着丝粒的远近 ,按由远到近的顺序在染色体上依次排列。HOXD基因簇中不同基因或其上游调控因子的重复或缺失都可能影响手指关节的发育 ,从而造成指 (趾 )数目或形态的异常。作者对湖南怀化地区一出生后即发现双手并指 ,双足并趾畸形患儿的常染色体显性先天性并指多指家系进行了连锁分析。结果显示 ,在SPD遗传基因座 2q31～q32发现紧密连锁 (两点间最大LOD :6 78;θ=0 0 0 )。多点连锁分析最大LOD值为 7 0 2。本家系单倍型分析遗传区间从D2s2 30 2到D2s315之间 ,间距为 2 0 6 1cM。我们对HOXD13基因的编码区 ,内含子 外显子交接区 ,和部分启动子区域进行序列分析未发现突变。结果证明了
Syndactyly is an autosomal dominant disorder characterized mainly by the development of hands and feet. The main clinical symptoms of the fingers connected by webbed. Which Ⅰ, Ⅱ, Ⅲ congenital and refers to the type located in the 2q34 ~ 36,2q31 ~ q32 and 6q2 1 ~ 2 3 2. And refers to the synaptic dactyly (SPD) is type Ⅱ and means (syndactyly, type Ⅱ), usually for the third and fourth fingers and 4,5 toes involved, between the two fingers (toes) connected by the web, Can not be separated. At present, the disease pathogenic gene HOXD13, located in 2q31 ~ q32. HOXD13 is located in the HOXD gene cluster. The 9 homologous genes (HOXD1, D3, D4, D8, D9, D10, D11, D12, D13) in the HOXD gene cluster are arranged on the chromosomes in ascending order according to their distance from the centromere . The duplication or deletion of different genes in the HOXD gene cluster or their upstream regulators may affect the development of the finger joints, resulting in an abnormal number or shape of the digits. The author of Hunan Huaihua area after the discovery of both hands and fingers, bipolar toe deformity in children with autosomal dominant congenital and refers to the multi-finger family linkage analysis. The results showed that in the SPD genetic locus 2q31 ~ q32 found a close linkage (maximum LOD between two points: 788; θ = 0 0 0). The maximum LOD value for multipoint analysis is 7 0 2. The haplotype analysis of this family had a genetic interval of D2s2302 to D2s315 with a spacing of 206i cM. We found no mutations in the HOXD13 gene coding region, intron exon transfer region, and partial promoter region sequence analysis. The result proved