Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment

J Hum Genet. 2018 Sep;63(9):1009-1013. doi: 10.1038/s10038-018-0477-0. Epub 2018 Jun 18.

Abstract

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.

Publication types

  • Clinical Trial

MeSH terms

  • Aldehyde Dehydrogenase / genetics*
  • Amino Acid Substitution
  • Cerebellar Ataxia / diagnostic imaging
  • Cerebellar Ataxia / genetics*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / genetics*
  • Female
  • Humans
  • Male
  • Mutation, Missense*
  • Spastic Paraplegia, Hereditary / diagnostic imaging
  • Spastic Paraplegia, Hereditary / genetics*

Substances

  • ALDH18A1 protein, human
  • Aldehyde Dehydrogenase