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

A Ciammola, P Carrera, A Di Fonzo, J Sassone, Roberta Villa, B Poletti, M Ferrari, Floriano Girotti, Edoardo Monfrini, G Buongarzone, V Silani, CM Cinnante, ML Mignogna, P D'Adamo, MT Bonati

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. © 2017 Elsevier Ltd.
Original languageEnglish
Pages (from-to)142-146
Number of pages5
JournalParkinsonism and Related Disorders
Volume44
Issue number3
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

Cite this

X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene. / Ciammola, A; Carrera, P; Di Fonzo, A; Sassone, J; Villa, Roberta; Poletti, B; Ferrari, M; Girotti, Floriano; Monfrini, Edoardo; Buongarzone, G; Silani, V; Cinnante, CM; Mignogna, ML; D'Adamo, P; Bonati, MT.

In: Parkinsonism and Related Disorders, Vol. 44, No. 3, 2017, p. 142-146.

Research output: Contribution to journalArticle

@article{21ef773f4fe940ca9494448f1b1b70c6,
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. {\circledC} 2017 Elsevier Ltd.",
author = "A Ciammola and P Carrera and {Di Fonzo}, A and J Sassone and Roberta Villa and B Poletti and M Ferrari and Floriano Girotti and Edoardo Monfrini and G Buongarzone and V Silani and CM Cinnante and ML Mignogna and P D'Adamo and MT Bonati",
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",
number = "3",

}

TY - JOUR

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

AU - Ciammola, A

AU - Carrera, P

AU - Di Fonzo, A

AU - Sassone, J

AU - Villa, Roberta

AU - Poletti, B

AU - Ferrari, M

AU - Girotti, Floriano

AU - Monfrini, Edoardo

AU - Buongarzone, G

AU - Silani, V

AU - Cinnante, CM

AU - Mignogna, ML

AU - D'Adamo, P

AU - Bonati, MT

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. © 2017 Elsevier Ltd.

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. © 2017 Elsevier Ltd.

U2 - 10.1016/j.parkreldis.2017.08.021

DO - 10.1016/j.parkreldis.2017.08.021

M3 - Article

VL - 44

SP - 142

EP - 146

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

IS - 3

ER -