Odake Yasuko, Koh Kishin, Takiyama Yoshihisa, Ishiura Hiroyuki, Tsuji Shoji, Yamada Masahito, Yoshita Mitsuhiro
Department of Clinical Research (Y.O., M. Yoshita), National Hospital Organization, Hokuriku National Hospital, Nanto; Department of Neurology (K.K., Y.T.), Graduate School of Medical Science, University of Yamanashi, Tyuo; Department of Neurology (H.I.), The University of Tokyo; Department of Molecular Neurology (S.T.), Graduate School of Medicine, The University of Tokyo; Institute of Medical Genomics (S.T.), International University of Health and Welfare, Chiba; and Department of Neurology and Neurobiology of Aging (M. Yamada), Kanazawa University Graduate School of Medical Sciences, Japan.
Neurol Genet. 2020 Sep 8;6(5):e514. doi: 10.1212/NXG.0000000000000514. eCollection 2020 Oct.
To establish molecular diagnosis for a family with a complicated form of autosomal recessive hereditary spastic paraplegia with intellectual disability, cognitive decline, psychosis, peripheral neuropathy, upward gaze palsy, and thin corpus callosum (TCC).
Physical examinations, laboratory tests, structural neuroimaging studies, and exome sequence analysis were carried out.
The 3 patients exhibited intellectual disability and progressive intellectual decline accompanied by psychiatric symptoms. Gait difficulty with spasticity and pyramidal weakness appeared at the ages of 20s-30s. Brain MRI revealed TCC with atrophic changes in the frontotemporal lobes, caudate nuclei, and cerebellum. Exome sequence analysis revealed a novel homozygous c.2654C>A (p. Ala885Asp) variant in the , a gene responsible for a complicated form of hereditary spastic paraplegia (SPG78), Kufor-Rakeb syndrome, and neuronal ceroid lipofuscinosis. The predominant clinical presentations of the patients include progressive intellectual disability and gait difficulty with spasticity and pyramidal weakness, consistent with the diagnosis of SPG78. Of note, prominent psychiatric symptoms and extrapyramidal signs including rigidity, dystonia, and involuntary movements preceded the spastic paraparesis.
Our study further broadens the clinical spectrum associated with mutations.
对一个患有复杂型常染色体隐性遗传性痉挛性截瘫的家系进行分子诊断，该家系患者伴有智力残疾、认知衰退、精神病、周围神经病变、向上凝视麻痹和胼胝体变薄（TCC）。
进行了体格检查、实验室检查、结构性神经影像学研究和外显子组序列分析。
3例患者表现出智力残疾和进行性智力衰退，并伴有精神症状。20多岁至30多岁时出现伴有痉挛和锥体束征的步态困难。脑部磁共振成像显示胼胝体变薄，额颞叶、尾状核和小脑有萎缩性改变。外显子组序列分析在 基因中发现了一个新的纯合c.2654C>A（p.Ala885Asp）变异，该基因与一种复杂型遗传性痉挛性截瘫（SPG78）、库福尔-拉凯布综合征和神经元蜡样脂褐质沉积症有关。患者的主要临床表现包括进行性智力残疾以及伴有痉挛和锥体束征的步态困难，符合SPG78的诊断。值得注意的是，在痉挛性截瘫之前出现了明显的精神症状和锥体外系体征，包括僵硬、肌张力障碍和不自主运动。
我们的研究进一步拓宽了与 突变相关的临床谱。
