Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1

Keivan Kaveh Moghadam, Fabio Pizza, Caterina Tonon, Raffaele Lodi, Valerio Carelli, Francesca Poli, Christian Franceschini, Piero Barboni, Marco Seri, Simona Ferrari, Chiara La Morgia, Claudia Testa, Ferdinando Cornelio, Rocco Liguori, Juliane Winkelmann, Ling Lin, Emmanuel Mignot, Giuseppe Plazzi

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. Methods: Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. Results: History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. Conclusions: The two asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS.

Original languageEnglish
Pages (from-to)582-585
Number of pages4
JournalSleep Medicine
Volume15
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • ADCA-DN
  • DNMT1
  • Genetic
  • MR spectroscopy
  • MSLT
  • Narcolepsy
  • Neurodegeneration

ASJC Scopus subject areas

  • Medicine(all)

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