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 journalArticlepeer-review


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
Number of pages5
JournalParkinsonism and Related Disorders
Publication statusPublished - Nov 2017


  • Journal Article


Dive into the research topics of 'X-linked Parkinsonism with Intellectual Disability caused by novel mutations and somatic mosaicism in RAB39B gene'. Together they form a unique fingerprint.

Cite this