Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism?

Arch Neurol. 2008 Apr;65(4):520-4. doi: 10.1001/archneur.65.4.520.

Abstract

Background: Hereditary spastic paraplegias (SPG1-SPG33) are characterized by progressive spastic weakness of the lower limbs. A nucleotide deletion (1110delA) in the (SPG20; OMIM 275900) spartin gene is the origin of autosomal recessive Troyer syndrome. This mutation is predicted to cause premature termination of the spartin protein. However, it remains unknown whether this truncated spartin protein is absent or is present and partially functional in patients.

Objective: To determine whether the truncated spartin protein is present or absent in cells derived from patients with Troyer syndrome.

Design: Case report.

Setting: Academic research.

Patients: We describe a new family with Troyer syndrome due to the 1110delA mutation.

Main outcome measures: We cultured primary fibroblasts and generated lymphoblasts from affected individuals, carriers, and control subjects and subjected these cells to immunoblot analyses.

Results: Spartin protein is undetectable in several cell lines derived from patients with Troyer syndrome.

Conclusions: Our data suggest that Troyer syndrome results from complete loss of spartin protein rather than from the predicted partly functional fragment. This may reflect increased protein degradation or impaired translation.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence / genetics
  • Cell Cycle Proteins
  • Consanguinity
  • Female
  • Fibroblasts / metabolism
  • Founder Effect
  • Frameshift Mutation
  • Gene Expression / genetics
  • Genetic Carrier Screening
  • Homozygote
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Neurologic Examination
  • Nucleotides / genetics
  • Pedigree
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Deletion*
  • Spastic Paraplegia, Hereditary / diagnosis
  • Spastic Paraplegia, Hereditary / genetics*
  • Syndrome

Substances

  • Cell Cycle Proteins
  • Nucleotides
  • Proteins
  • SPART protein, human