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 journalArticle

4 Citations (Scopus)

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

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DNA (Cytosine-5-)-Methyltransferase
Sleep
REM Sleep
Mutation
Genes
Neurologic Examination
Inositol
Neurodegenerative Diseases
History
Brain
Nuclear Family
Point Mutation
Neuroimaging
Neuroglia
Magnetic Resonance Spectroscopy
Central Nervous System
Cell Count
Magnetic Resonance Imaging
Cerebellar Ataxia, Deafness, and Narcolepsy

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

In: Sleep Medicine, Vol. 15, No. 5, 2014, p. 582-585.

Research output: Contribution to journalArticle

Moghadam, Keivan Kaveh ; Pizza, Fabio ; Tonon, Caterina ; Lodi, Raffaele ; Carelli, Valerio ; Poli, Francesca ; Franceschini, Christian ; Barboni, Piero ; Seri, Marco ; Ferrari, Simona ; La Morgia, Chiara ; Testa, Claudia ; Cornelio, Ferdinando ; Liguori, Rocco ; Winkelmann, Juliane ; Lin, Ling ; Mignot, Emmanuel ; Plazzi, Giuseppe. / 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. In: Sleep Medicine. 2014 ; Vol. 15, No. 5. pp. 582-585.
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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.",
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T1 - 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

AU - Moghadam, Keivan Kaveh

AU - Pizza, Fabio

AU - Tonon, Caterina

AU - Lodi, Raffaele

AU - Carelli, Valerio

AU - Poli, Francesca

AU - Franceschini, Christian

AU - Barboni, Piero

AU - Seri, Marco

AU - Ferrari, Simona

AU - La Morgia, Chiara

AU - Testa, Claudia

AU - Cornelio, Ferdinando

AU - Liguori, Rocco

AU - Winkelmann, Juliane

AU - Lin, Ling

AU - Mignot, Emmanuel

AU - Plazzi, Giuseppe

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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KW - MR spectroscopy

KW - MSLT

KW - Narcolepsy

KW - Neurodegeneration

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