Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.
Department of Neurology, The University of Tokyo, Tokyo, Japan.
J Hum Genet. 2022 Feb;67(2):119-121. doi: 10.1038/s10038-021-00977-z. Epub 2021 Sep 6.
Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chédiak-Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.
遗传性痉挛性截瘫(HSPs)是一组以无力和腿部痉挛为特征的神经退行性疾病。LYST 负责 Chédiak-Higashi 综合征(CHS),其在儿童时期表现为部分眼皮肤白化病、原发性免疫缺陷和出血倾向。尽管 CHS 的神经症状也出现在成年期,但 CHS 中很少有痉挛性截瘫表型的报道。在这项研究中,我们通过日本痉挛性截瘫研究联合会(Japan Spastic Paraplegia Research Consortium)调查了 387 名 HSP 患者中的 LYST 突变,以明确 LYST 突变在 HSP 中的频率,发现了四个 HSP 家系中的六位成年 LYST 突变患者。他们表现出智力障碍、小脑共济失调、神经病和锥体束征。同时,在日本的一项全国性调查中,仅在过去十年中发现了 15 例儿童期 CHS 患者。因此,在相当数量的成年 CHS 患者中,LYST 突变可能提示 HSP 表型。