Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.
Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan.
J Hum Genet. 2018 Sep;63(9):1009-1013. doi: 10.1038/s10038-018-0477-0. Epub 2018 Jun 18.
Hereditary spastic paraplegias (HSPs) are characterized by various inherited disorders in which weakness and spasticity of the lower extremities are the predominant symptoms. Recently, HSP caused by ALDH18A1 mutations has been reported as SPG9 with autosomal dominant (SPG9A) and autosomal recessive (SPG9B) transmission. In this study, we obtained clinical and genetic findings in two Japanese families with SPG9B. One family had a novel compound heterozygous mutation (c.1321 C > T/c.1994G > A) in the ALDH18A1 gene. The other family had a homozygous mutation (c.383 G > A/c.383 G > A) in the ALDH18A1 gene. To date, only two SPG9B families with ALDH18A1 mutations have been reported. This is the first report of SPG9 in non-Caucasians. Furthermore, we found cerebellar ataxia in one family, although cerebellar ataxia has not been reported in SPG9B so far. SPG9B might involve a complicated HSP including cerebellar ataxia and cognitive impairment. This study expands the clinical and genetic spectrum of ALDH18A1-related disorders.
遗传性痉挛性截瘫（HSP）的特征是各种遗传性疾病，以下肢无力和痉挛为主要症状。最近，报道了由 ALDH18A1 突变引起的 HSP 为 SPG9，呈常染色体显性（SPG9A）和常染色体隐性（SPG9B）遗传。本研究在两个具有 SPG9B 的日本家族中获得了临床和遗传发现。一个家族在 ALDH18A1 基因中存在新的复合杂合突变（c.1321C>T/c.1994G>A）。另一个家族在 ALDH18A1 基因中存在纯合突变（c.383G>A/c.383G>A）。迄今为止，仅报道了两个具有 ALDH18A1 突变的 SPG9B 家族。这是首例非高加索人群中的 SPG9 报道。此外，我们发现一个家族存在小脑性共济失调，尽管迄今为止尚未报道 SPG9B 存在小脑性共济失调。SPG9B 可能涉及包括小脑性共济失调和认知障碍在内的复杂 HSP。本研究扩展了与 ALDH18A1 相关疾病的临床和遗传谱。
