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

doi:10.1016/j.parkreldis.2017.08.021

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 journal › Article › peer-review

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 language	English
Pages (from-to)	142-146
Number of pages	5
Journal	Parkinsonism and Related Disorders
Volume	44
DOIs	https://doi.org/10.1016/j.parkreldis.2017.08.021
Publication status	Published - Nov 2017

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Ciammola, A., Carrera, P., Di Fonzo, A., Sassone, J., Villa, R., Poletti, B., Ferrari, M., Girotti, F., Monfrini, E., Buongarzone, G., Silani, V., Cinnante, C. M., Mignogna, M. L., D'Adamo, P., & Bonati, M. T. (2017). X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene. Parkinsonism and Related Disorders, 44, 142-146. https://doi.org/10.1016/j.parkreldis.2017.08.021

X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene. / Ciammola, Andrea ; Carrera, Paola ; Di Fonzo, Alessio; Sassone, Jenny; Villa, Roberta; Poletti, Barbara ; Ferrari, Maurizio; Girotti, Floriano; Monfrini, Edoardo; Buongarzone, Gabriele; Silani, Vincenzo ; Cinnante, Claudia Maria; Mignogna, Maria Lidia; D'Adamo, Patrizia ; Bonati, Maria Teresa.

In: Parkinsonism and Related Disorders, Vol. 44, 11.2017, p. 142-146.

Research output: Contribution to journal › Article › peer-review

Ciammola, A , Carrera, P , Di Fonzo, A, Sassone, J, Villa, R, Poletti, B , Ferrari, M, Girotti, F, Monfrini, E, Buongarzone, G, Silani, V , Cinnante, CM, Mignogna, ML, D'Adamo, P & Bonati, MT 2017, 'X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene', Parkinsonism and Related Disorders, vol. 44, pp. 142-146. https://doi.org/10.1016/j.parkreldis.2017.08.021

Ciammola, Andrea ; Carrera, Paola ; Di Fonzo, Alessio ; Sassone, Jenny ; Villa, Roberta ; Poletti, Barbara ; Ferrari, Maurizio ; Girotti, Floriano ; Monfrini, Edoardo ; Buongarzone, Gabriele ; Silani, Vincenzo ; Cinnante, Claudia Maria ; Mignogna, Maria Lidia ; D'Adamo, Patrizia ; Bonati, Maria Teresa. / X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene. In: Parkinsonism and Related Disorders. 2017 ; Vol. 44. pp. 142-146.

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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.",

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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}",

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doi = "10.1016/j.parkreldis.2017.08.021",

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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 - 2017/11

Y1 - 2017/11

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.

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DO - 10.1016/j.parkreldis.2017.08.021

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