Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis.
Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis.
复制标题
DOI：
10.1534/g3.114.015669
复制
发表时间：
2014-12-12
期刊：
影响因子：
--
通讯作者：
Miller NH
中科院分区：
文献类型：
--
作者：
Baschal EE;Wethey CI;Swindle K;Baschal RM;Gowan K;Tang NL;Alvarado DM;Haller GE;Dobbs MB;Taylor MR;Gurnett CA;Jones KL;Miller NH
特发性脊柱侧凸发生在3%的个体中，病因不明。这项研究的目的是通过在一个多代特发性脊柱侧凸家系中使用外显子组测序来识别与特发性脊柱侧凸病因有关的罕见变异。对这个患有特发性脊柱侧弯的多代家庭中的三名成员进行了外显子组测序，结果确定HSPG2基因的一个变异是该表型的潜在贡献者。对100名患有特发性脊柱侧弯的无关个体进行了HSPG2基因测序，并在独立的特发性脊柱侧凸人群中进行了检测。外显子组测序和随后的生物信息学过滤导致了16个潜在的破坏性和稀有的编码变体。其中一个变异体p.Asn786Ser位于HSPG2基因中。与对照人群相比，P.Asn786Ser变异在特发性脊柱侧凸患者队列中也有过高的表达(P=0.024)。此外，我们还发现了另外一些罕见的HSPG2变异，这些变异被预测在两个独立的特发性脊柱侧凸患者队列中具有破坏性。HSPG2基因编码一种在细胞外基质中普遍存在的多功能蛋白，其中功能突变的丢失已知会导致小鼠和人类的肌肉骨骼表型。根据这些结果，我们得出结论，在特发性脊柱侧凸患者中，HSPG2基因的罕见变异可能与特发性脊柱侧凸的表型有关。HSPG2基因对特发性脊柱侧弯表型的影响还有待进一步研究。
Idiopathic scoliosis occurs in 3% of individuals and has an unknown etiology. The objective of this study was to identify rare variants that contribute to the etiology of idiopathic scoliosis by using exome sequencing in a multigenerational family with idiopathic scoliosis. Exome sequencing was completed for three members of this multigenerational family with idiopathic scoliosis, resulting in the identification of a variant in the HSPG2 gene as a potential contributor to the phenotype. The HSPG2 gene was sequenced in a separate cohort of 100 unrelated individuals affected with idiopathic scoliosis and also was examined in an independent idiopathic scoliosis population. The exome sequencing and subsequent bioinformatics filtering resulted in 16 potentially damaging and rare coding variants. One of these variants, p.Asn786Ser, is located in the HSPG2 gene. The variant p.Asn786Ser also is overrepresented in a larger cohort of idiopathic scoliosis cases compared with a control population (P = 0.024). Furthermore, we identified additional rare HSPG2 variants that are predicted to be damaging in two independent cohorts of individuals with idiopathic scoliosis. The HSPG2 gene encodes for a ubiquitous multifunctional protein within the extracellular matrix in which loss of function mutation are known to result in a musculoskeletal phenotype in both mouse and humans. Based on these results, we conclude that rare variants in the HSPG2 gene potentially contribute to the idiopathic scoliosis phenotype in a subset of patients with idiopathic scoliosis. Further studies must be completed to confirm the effect of the HSPG2 gene on the idiopathic scoliosis phenotype.
登录
查看更多内容
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1186/1748-7161-1-2
发表时间：
2006-03-31
期刊：
Scoliosis
影响因子：
--
作者：
Asher MA;Burton DC
通讯作者：
Burton DC
影响因子：
9.8
作者：
Arikawa-Hirasawa, E;Le, AH;Yamada, Y
通讯作者：
Yamada, Y
影响因子：
3
作者：
Clough, Mark;Justice, Cristina M.;Miller, Nancy H.
通讯作者：
Miller, Nancy H.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--