Clinical features of homozygous FIG4-p.Ile41Thr Charcot-Marie-Tooth 4J patients

Ann Clin Transl Neurol. 2021 Feb;8(2):471-476. doi: 10.1002/acn3.51175. Epub 2021 Jan 6.

Abstract

We describe the clinical, electrodiagnostic, and genetic findings of three homozygous FIG4-c.122T>C patients suffering from Charcot-Marie-Tooth disease type 4J (AR-CMT-FIG4). This syndrome usually involves compound heterozygosity associating FIG4-c.122T>C, a hypomorphic allele coding an unstable FIG4-p.Ile41Thr protein, and a null allele. While the compound heterozygous patients presenting with early onset usually show rapid progression, the homozygous patients described here show the signs of relative clinical stability. As FIG4 activity is known to be dose dependent, these patients' observations could suggest that the therapeutic perspective of increasing levels of the protein to improve the phenotype of AR-CMT-FIG4-patients might be efficient.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / physiopathology*
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / physiopathology
  • Flavoproteins / genetics*
  • Genetic Testing
  • Genotype
  • Homozygote
  • Humans
  • Inheritance Patterns
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mutation
  • Phenotype
  • Phosphoric Monoester Hydrolases / genetics*

Substances

  • Flavoproteins
  • Intracellular Signaling Peptides and Proteins
  • FIG4 protein, human
  • Phosphoric Monoester Hydrolases

Supplementary concepts

  • Charcot-Marie-Tooth Disease, Type 4j