Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome
Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome
复制标题
DOI：
10.1016/j.ajhg.2008.06.023
复制
发表时间：
2008-08-08
影响因子：
9.8
通讯作者：
Gleeson, Joseph G.
中科院分区：
文献类型：
--
作者：
Cantagrel, Vincent;Silhavy, Jennifer L.;Gleeson, Joseph G.
Joubert 综合征（美国）及相关疾病是一组常染色体隐性遗传疾病，在轴位脑 MRI 上具有“磨牙征”，同时伴有小脑蚓部发育不全、共济失调和精神运动迟缓。 JS 被认为是一种纤毛功能障碍，是涉及视网膜、肾脏、指、口腔、肝脏和大脑器官的一系列疾病的一部分。我们在两个具有 JS 经典形式的家族中发现了 ARL13B 突变。 ARL13B 属于 Ras GTPase 家族，在其他物种中是纤毛发生、体轴形成和肾功能所必需的。编码的 Arl13b 蛋白在发育中的小鼠小脑中表达，并定位于初级神经元的纤毛。人类野生型而非患者突变体 ARL13B 的过度表达拯救了 Arl13b 蝎子斑马鱼突变体。因此，ARL13B 在多个器官中具有介导纤毛功能的进化保守作用。
Joubert syndrome US) and related disorders are a group of autosomal-recessive conditions sharing the "molar tooth sign" on axial brain MRI, together with cerebellar vermis hypoplasia, ataxia, and psychomotor delay. JS is suggested to be a disorder of cilia function and is part of a spectrum of disorders involving retinal, renal, digital, oral, hepatic, and cerebral organs. We identified mutations in ARL13B in two families with the classical form of JS. ARL13B belongs to the Ras GTPase family, and in other species is required for ciliogenesis, body axis formation, and renal function. The encoded Arl13b protein was expressed in developing murine cerebellum and localized to the cilia in primary neurons. Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs.