A pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2 causing spastic paraplegia 77

Ann Clin Transl Neurol. 2024 Nov;11(11):3019-3024. doi: 10.1002/acn3.52195. Epub 2024 Sep 28.

Abstract

FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alu Elements* / genetics
  • Exons* / genetics
  • Female
  • Humans
  • Male
  • Mitochondrial Proteins
  • Mutation, Missense*
  • Pedigree
  • Phenylalanine-tRNA Ligase / genetics
  • Sequence Deletion / genetics
  • Spastic Paraplegia, Hereditary* / genetics
  • Spastic Paraplegia, Hereditary* / physiopathology

Substances

  • FARS2 protein, human
  • Phenylalanine-tRNA Ligase
  • Mitochondrial Proteins