Sequencing of the TBX6 Gene in Families with Familial Idiopathic Scoliosis.
Sequencing of the TBX6 Gene in Families with Familial Idiopathic Scoliosis.
复制标题
在具有家族特发性脊柱侧弯家族中TBX6基因的测序。
DOI：
10.1016/j.jspd.2015.01.005
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发表时间：
2015-07
期刊：
影响因子：
1.6
通讯作者：
中科院分区：
文献类型：
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作者：
在一个家族性队列中进行了一项假设驱动的研究，以确定TBX6基因变异与家族性特发性脊柱侧凸(FIS)之间的潜在关联。目的：确定在FIS家系样本中，TBX6基因外显子内的变异是否与FIS表型分离。特发性脊柱侧凸(IS)是脊柱的一种结构性弯曲，其潜在的遗传病因尚未确定。据报道，在先天性脊柱侧弯(CS)患者的家庭成员中，IS的发生率高于预期，这表明这两种疾病可能有相同的病因。染色体16p上的TBX6基因是体节发育所必需的，在中国人群中与CS相关。以前的研究已经在FIS家系中发现了与该基因的连锁，特别是与位于TBX6基因内含子上的rs8060511连锁。对来自11个FIS家系(13个三联体，42个个体)的亲子三人进行了Tbx6基因的Sanger测序。三个人是从一大群患有FIS的家庭中挑选出来的，在这些家庭中，全基因组扫描导致了与16P的连锁。对家族子集的测序分析导致识别出五个编码变体。五个变异体中有三个是新的；其余两个变异体是先前确定的，占这三个变异体中观察到的变异体的90%。在所有病例中，TBX6变异等位基因的传播与FIS表型之间没有相关性。然而，对成骨细胞中的调节标志物的分析表明，rs8060511是一个假定的增强子元件。虽然这项研究没有发现任何与FIS分离的TBX6编码变体，但我们发现了一个位于潜在的TBX6增强子元件中的变体。因此，有必要对该地区进行进一步调查。
A hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within the TBX6 gene and Familial Idiopathic Scoliosis (FIS). To determine if variants within exons of the TBX6 gene segregate with the FIS phenotype within a sample of families with FIS. Idiopathic Scoliosis (IS) is a structural curvature of the spine whose underlying genetic etiology has not been established. IS has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis (CS), suggesting that the two diseases might have a shared etiology. The TBX6 gene on chromosome 16p, essential to somite development, has been associated with CS in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of the TBX6 gene. Parent-offspring trios from 11 families (13 trios, 42 individuals) with FIS were selected for Sanger sequencing of the TBX6 gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p. Sequencing analyses of the subset of families resulted in the identification of five coding variants. Three of the five variants were novel; the remaining two variants were previously characterized and account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of the TBX6 variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element. Although this study did not identify any TBX6 coding variants that segregate with FIS, we identified a variant that is located in a potential TBX6 enhancer element. Therefore, further investigation of the region is needed.