Mutations in BOREALIN cause thyroid dysgenesis
Mutations in BOREALIN cause thyroid dysgenesis
复制标题
DOI：
10.1093/hmg/ddw419
复制
发表时间：
2017-02-01
影响因子：
3.5
通讯作者：
Polak, Michel
中科院分区：
文献类型：
--
作者：
Carre, Aurore;Stoupa, Athanasia;Polak, Michel
先天性甲状腺功能减退症是最常见的新生儿内分泌紊乱，主要由发育异常引起，也称为甲状腺发育不良（TD）。我们在一个患有TD的近亲家庭中进行了全外显子组测序（WES），随后对134个患有TD的先显子进行了测序，以确定易患该疾病的遗传因素。我们在td患者家庭中发现了新的错义突变p.S148F、p.R114Q和p.L177Win。Borealin是染色体乘客复合体（CPC）的主要组成部分，在有丝分裂中具有众所周知的功能。进一步分析错义突变对有丝分裂没有明显影响。相反，在人甲状腺细胞中表达突变体导致粘附和迁移缺陷，相应的基因表达变化表明该有丝分裂蛋白具有其他功能。这些结果与BOREALIN-p.R114W患者甲状腺组织中分析的相同基因表达模式密切相关。这些研究为研究人类TD的遗传学开辟了新的途径。
Congenital hypothyroidism is the most common neonatal endocrine disorder and is primarily caused by developmental abnormalities otherwise known as thyroid dysgenesis (TD). We performed whole exome sequencing (WES) in a consanguineous family with TD and subsequently sequenced a cohort of 134 probands with TD to identify genetic factors predisposing to the disease. We identified the novel missense mutations p.S148F, p.R114Q and p.L177Win the BOREALIN gene in TD-affected families. Borealin is a major component of the Chromosomal Passenger Complex (CPC) with well-known functions in mitosis. Further analysis of the missense mutations showed no apparent effects on mitosis. In contrast, expression of the mutants in human thyrocytes resulted in defects in adhesion and migration with corresponding changes in gene expression suggesting others functions for this mitotic protein. These results were well correlated with the same gene expression pattern analysed in the thyroid tissue of the patient with BOREALIN-p.R114W. These studies open new avenues in the genetics of TD in humans.