A novel homozygous KY variant causing a complex neurological disorder

Eur J Med Genet. 2020 Nov;63(11):104031. doi: 10.1016/j.ejmg.2020.104031. Epub 2020 Aug 18.


Mutations in the gene kyphoscoliosis peptidase (KY) are known to cause myofibrillar myopathy-7 and hereditary spastic paraplegia. We investigated the genetic cause of a complex neurological phenotype in a consanguineous Pakistani family with four affected members, manifesting lower limb spasticity and weakness, toe walking, pes equinovarus, and a speech disorder. Genome-wide linkage analysis with microsatellite markers delineated chromosome 3q22.2-q24 harboring the disease gene. Whole exome sequencing was performed for two subjects, identifying a homozygous 14-bp frameshift deletion NM_178554.6:c.842_855del; p(Val281GlyfsTer18) in KY. The variant segregated with the phenotype and was absent from public databases and 100 ethnically matched controls. We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family. A review of previously reported KY variants suggests that variants in this gene can cause a spectrum of neurological phenotypes.

Keywords: Hereditary spastic paraplegia; KY; Kyphoscoliosis peptidase; Pesequinovarus; Speech disorder.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Female
  • Frameshift Mutation
  • Gait
  • Homozygote
  • Humans
  • Male
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology
  • Pedigree
  • Peptide Hydrolases / genetics*
  • Phenotype*
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology
  • Speech


  • KY protein, human
  • Peptide Hydrolases

Supplementary concepts

  • Myofibrillar Myopathy