Okamoto Nobuhiko, Miya Fuyuki, Tsunoda Tatsuhiko, Yanagihara Keiko, Kato Mitsuhiro, Saitoh Shinji, Yamasaki Mami, Kanemura Yonehiro, Kosaki Kenjiro
Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
Laboratory for Medical Science Mathematics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
J Hum Genet. 2014 Nov;59(11):639-41. doi: 10.1038/jhg.2014.80. Epub 2014 Sep 25.
Kinesins are a large superfamily of molecular motors. They move along microtubule filaments and are powered by the hydrolysis of ATP. This transport system is essential for neuronal function and survival. KIF1A belongs to the kinesin 3 family and involves in the anterograde transport of synaptic vesicle precursors along axons. Several studies confirmed that KIF1A mutations cause spastic paraplegia and sensory neuropathy in an autosomal-recessive fashion. A missense mutation in the KIF1A gene (p.Thr99Met) has been reported in a patient with intellectual disability (ID), axial hypotonia and peripheral spasticity. Mild atrophy of the cerebellar vermis was found on magnetic resonance imaging. The mutation was heterozygous and de novo. We identified the second patient with the p.T99M mutation in the KIF1A gene by whole-exome sequencing. He showed severe ID, spasticity, optic atrophy, neurogenic bladder, growth failure and progressive cerebellar atrophy. The p.T99M mutation may be a common recurrent mutation. We suppose that this specific mutation of KIF1A shows a novel neurodegenerative syndrome.
驱动蛋白是一个庞大的分子马达超家族。它们沿着微管丝移动，并由ATP水解提供动力。这种运输系统对神经元功能和存活至关重要。KIF1A属于驱动蛋白3家族，参与突触小泡前体沿轴突的顺行运输。多项研究证实，KIF1A突变以常染色体隐性方式导致痉挛性截瘫和感觉神经病变。一名患有智力残疾（ID）、轴向肌张力减退和周围性痉挛的患者中报告了KIF1A基因的一个错义突变（p.Thr99Met）。磁共振成像发现小脑蚓部轻度萎缩。该突变是杂合性且为新发突变。我们通过全外显子组测序鉴定出了第二例携带KIF1A基因p.T99M突变的患者。他表现出严重的ID、痉挛、视神经萎缩、神经源性膀胱、生长发育迟缓以及进行性小脑萎缩。p.T99M突变可能是一种常见的反复出现的突变。我们推测KIF1A的这种特定突变表现出一种新型神经退行性综合征。
