A novel homozygous FBXO38 variant causes an early-onset distal hereditary motor neuronopathy type IID

J Hum Genet. 2019 Nov;64(11):1141-1144. doi: 10.1038/s10038-019-0652-y. Epub 2019 Aug 17.


Distal hereditary motor neuronopathies (dHMN) are a genetically heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and progressive distal muscle weakness. A heterozygous missense variant in FBXO38 has been previously described in two families affected by autosomal-dominant dHMN. In this paper, we describe a homozygous missense variant in FBXO38 (c.1577G>A; p.(Arg526Gln)) in a young Turkish female, offspring of consanguineous parents, with a congenital mild neuronopathy with idiopathic toe walking, normal sensory examination, and hearing loss. This work is the first to describe a novel homozygous variant and a suggested loss of function mechanism in FBXO38, expanding the dHMN type IID phenotype.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • F-Box Proteins / genetics*
  • Female
  • Genetic Heterogeneity
  • Heterozygote
  • Homozygote
  • Humans
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / physiopathology
  • Mutation, Missense / genetics
  • Pedigree
  • Phenotype
  • Young Adult


  • F-Box Proteins
  • FBXO38 protein, human

Supplementary concepts

  • Distal Hereditary Motor Neuropathy, Type II