一先天性并指中国家系的遗传学研究  

Genetic Analysis of a Chinese Pedigree with Congenital Synpolydactyly

作　　者：秦炜[1] 舒安利 邢清和[1] 秧茂盛[1] 冯国鄞[1] 贺林[3] 

机构地区：[1]中国科学院上海生命科学研究院营养科学研究所,上海,200031,上海交通大学Bio-X生命科学研究中心,上海,200030 [2]湖南怀化医学专科学校,湖南怀化,418000 [3]上海交通大学Bio-X生命科学研究中心,上海,200030,中国科学院上海生命科学研究院营养科学研究所,上海,200031

出　　处：《Acta Genetica Sinica》2003年第10期973-977,共5页

基　　金：国家 973基金 (0 0 1CB5 10 3 0 1);国家科技攻关计划 (2 0 0 2BA711A0 7)资助项目~~

摘　　要：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。Syndactyly is a limb malformation that shows a ch aracteristic manifes tation in both hands and feet.This condition is inherited as an autosomal domina nt trait with reduced penetrance.Clinical presentation,in general,is complete or partial webbing between 3rd and 4th fingers.Syndactyly type Ⅰ,Ⅱand Ⅲwere mapped to 2q34-36,2q31-q32 and 6q21-23.2 respectively.Syndactyly type Ⅱis n amed as synpolydactyly (SPD).Expansion of a polyalanine tract in the HOXD13 gene is known to cause synpolydactyly.HOXD13 gene locates in the HoxD complex.Nine homologous genes (HOXD1,-D3,-D4,-D8,-D9,-D10,-D11,-D12, -D13) of HoxD complex locate on chromosome 2 in the order o f HOXD1 to HOXD13,among which HOXD13 is closest to the centromere.Deletions and duplications in HoxD complex or its upstream regulator factors have been identified to cause hand heteroplasia and consequently lead to abnormity of finger number or abnormity of configuration.W e performed linkage analysis in a kindred with autosomal dominant hereditary syn dactyly.Tight linkage to markers on chromosome 2q31-q32 (maximum two-point lod score:6.78 at recombination fraction θ=0.00) was observed.Multipoint li nkage analysis produced a maximum LOD score of 7.02.Haplotype construction and analysi s of recombination events narrowed this locus to a 20.61 cM region between marke rs D2S2302 and D2S315.No mutation was found in the coding region,the intron-ex on boundaries,or part of the promoter region of HOXD13 .Our result demonstrates that synpolydactyly locus in the Chinese Han Population is in the region of chr omosome 2q31-q32 but a different causal gene can be involved.

关 键 词：并指 并指多指 连锁分析 表型 

分 类 号：R596.1[医药卫生—内科学]