Joubert syndrome: congenital cerebellar ataxia with the molar tooth.
Joubert syndrome: congenital cerebellar ataxia with the molar tooth.
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DOI：
10.1016/s1474-4422(13)70136-4
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发表时间：
2013-09
期刊：
影响因子：
48
通讯作者：
Valente, Enza Maria
中科院分区：
文献类型：
--
作者：
Romani, Marta;Micalizzi, Alessia;Valente, Enza Maria
Joubert综合征（JS）是一种常染色体隐性遗传或X连锁遗传的先天性小脑共济失调，其诊断标志是在脑影像学上可识别的独特的小脑和脑干畸形，即“臼齿征”。神经系统体征从新生儿开始出现，包括张力减退演变为共济失调、全面发育迟缓、眼运动性失用症和呼吸失调。这些疾病与多器官受累有关，主要是视网膜、肾脏、骨骼和肝脏。到目前为止，已经确定了21个致病基因，所有编码的蛋白质的初级纤毛或其装置。这是一种亚细胞细胞器，在发育和许多细胞功能中发挥关键作用，使JS成为不断扩大的纤毛病家族的一部分。在不同的纤毛病之间有明显的临床和遗传重叠，甚至在家族内也可能共同发生。这种变异性可能是由遗传的寡基因模型解释的，其中不同基因座的突变、罕见变体和多态性相互作用以调节纤毛表型的表达性。
Joubert syndrome (JS) is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, which diagnostic hallmark is a unique cerebellar and brainstem malformation recognizable on brain imaging, the “molar tooth sign”. Neurological signs are present from neonatal age and include hypotonia evolving into ataxia, global developmental delay, ocular motor apraxia and breathing dysregulation. These are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton and liver. To date, 21 causative genes have been identified, all encoding for proteins of the primary cilium or its apparatus. This is a subcellular organelle that plays key roles in development and in many cellular functions, making JS part of the expanding family of ciliopathies. There is marked clinical and genetic overlap among distinct ciliopathies, which may co-occur even within families. Such variability is likely explained by an oligogenic model of inheritance, in which mutations, rare variants and polymorphisms at distinct loci interplay to modulate the expressivity of the ciliary phenotype.