X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene

Andrea Ciammola, Paola Carrera, Alessio Di Fonzo, Jenny Sassone, Roberta Villa, Barbara Poletti, Maurizio Ferrari, Floriano Girotti, Edoardo Monfrini, Gabriele Buongarzone, Vincenzo Silani, Claudia Maria Cinnante, Maria Lidia Mignogna, Patrizia D'Adamo, Maria Teresa Bonati

Research output: Contribution to journalArticle

Abstract

Background: RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts.In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. Methods: Three patients received neurological evaluation and underwent RAB39B sequencing. Results: Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. Conclusion: In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.

Original languageEnglish
Pages (from-to)142-146
JournalParkinsonism and Related Disorders
Volume44
DOIs
Publication statusPublished - 2017

Fingerprint

Mosaicism
Parkinsonian Disorders
Intellectual Disability
Globus Pallidus
Tremor
Neuroimaging
Mutation
Pulvinar
Genes
Red Nucleus
Exome
Hypokinesia
Putamen
Substantia Nigra
Parkinson Disease
Proteins

Keywords

  • Intellectual Disability
  • Parkinsonism
  • RAB39B
  • Somatic mosaicism

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

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title = "X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene",
abstract = "Background: RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts.In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. Methods: Three patients received neurological evaluation and underwent RAB39B sequencing. Results: Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. Conclusion: In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.",
keywords = "Intellectual Disability, Parkinsonism, RAB39B, Somatic mosaicism",
author = "Andrea Ciammola and Paola Carrera and {Di Fonzo}, Alessio and Jenny Sassone and Roberta Villa and Barbara Poletti and Maurizio Ferrari and Floriano Girotti and Edoardo Monfrini and Gabriele Buongarzone and Vincenzo Silani and Cinnante, {Claudia Maria} and Mignogna, {Maria Lidia} and Patrizia D'Adamo and Bonati, {Maria Teresa}",
year = "2017",
doi = "10.1016/j.parkreldis.2017.08.021",
language = "English",
volume = "44",
pages = "142--146",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene

AU - Ciammola, Andrea

AU - Carrera, Paola

AU - Di Fonzo, Alessio

AU - Sassone, Jenny

AU - Villa, Roberta

AU - Poletti, Barbara

AU - Ferrari, Maurizio

AU - Girotti, Floriano

AU - Monfrini, Edoardo

AU - Buongarzone, Gabriele

AU - Silani, Vincenzo

AU - Cinnante, Claudia Maria

AU - Mignogna, Maria Lidia

AU - D'Adamo, Patrizia

AU - Bonati, Maria Teresa

PY - 2017

Y1 - 2017

N2 - Background: RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts.In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. Methods: Three patients received neurological evaluation and underwent RAB39B sequencing. Results: Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. Conclusion: In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.

AB - Background: RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome sequencing in large Parkinson's disease cohorts.In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability. Methods: Three patients received neurological evaluation and underwent RAB39B sequencing. Results: Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi. Conclusion: In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.

KW - Intellectual Disability

KW - Parkinsonism

KW - RAB39B

KW - Somatic mosaicism

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