Identification of FXTAS presenting with SCA 12 like phenotype in India

Parkinsonism Relat Disord. 2014 Oct;20(10):1089-93. doi: 10.1016/j.parkreldis.2014.07.001. Epub 2014 Jul 17.

Abstract

Background: Fragile X-associated Tremor/Ataxia syndrome (FXTAS) is a clinically heterogeneous disorder characterized predominantly by tremor, followed by late onset gait ataxia, autonomic dysfunction and/or cognitive impairment. We aimed to screen FMR1-CGG repeats in our cohort of progressive late-onset cerebellar ataxia/tremor cohort to characterize the occurrence of FXTAS in India.

Methods: We have screened FMR1-CGG repeats in 109 patients and 173 healthy control subjects. Our cohort comprised: a)group of patients with predominant cerebellar ataxia and/or tremor. b.)suspected cases of MSA and c.)patients who presented SCA12-like neurological manifestations (late onset predominant tremor and/or ataxia). All the cases were ruled out for known triplet-repeat-expansion (TRE) SCA mutations.

Results: We have found three FMR1-premutation carriers among the cases. Two of them (with CGG-96 and CGG-102) were under evaluation for their SCA12-like manifestations and another (CGG-78) had progressive gait ataxia. Overall the frequency of FXTAS in our cohort was found to be 3.3% among cases of late onset cerebellar-ataxia/tremor; however, incidences were higher among cases with SCA12-like syndrome (9%, 2/23).

Conclusion: Finding FXTAS in patients with SCA12-like manifestation suggests that TRE in the 5'UTR of the gene is the common cue connecting two disorders with common phenotype of tremor/ataxia. This knowledge might shed light upon their sharing of molecular neuropathology.

Keywords: FXTAS; SCA12; Tremor and ataxia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Aged
  • Aged, 80 and over
  • Ataxia / diagnosis*
  • Ataxia / genetics*
  • Cohort Studies
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics*
  • Humans
  • India / epidemiology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Phenotype
  • Protein Phosphatase 2 / genetics
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / physiopathology*
  • Tremor / diagnosis*
  • Tremor / genetics*
  • Trinucleotide Repeats / genetics*

Substances

  • FMR1 protein, human
  • Nerve Tissue Proteins
  • Fragile X Mental Retardation Protein
  • PPP2R2B protein, human
  • Protein Phosphatase 2

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome