Parkinson Disease and Complex Parkinsonism

Gene: RAB39B

Green List (high evidence)

X linked hemizygous in males, monoallelic in females may cause mild features described in males/females with ID and PD. PMID 25434005 (2 families with early-onset parkinsonism and intellectual disability, pathologically confirmed Parkinson disease), 26399558 (1 family with X linked dominant PD, female with reduced penetrance), 27066548 (1 male with typical PD). Mutations also cause X-linked ID. PMID 20159109 (2 male pts from 2 families with X-linked mental retardation associated with autism, epilepsy, and macrocephaly.

Created: 14 Dec 2016, 5:27 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
early-onset parkinsonism and intellectual disability

Publications

• 25434005
• 26399558
• 27066548

PMID:2639955 identified a missense mutation (c.574G > A; p.G192R, rs864309527) in the RAB39B gene that closely segregated with Parkinson's disease and exhibited X-linked dominant inheritance with reduced penetrance in females. Three unaffected females aged 40, 55 and 86 years, and a 41-year-old unaffected male, also carried the G192R mutation. The mutation p.G192R resulted in mislocalization of the mutant protein.

Created: 10 Nov 2016, 4:25 p.m.

Comment on mode of inheritance: Changed to monoallelic in females as one case reported.

Created: 8 Dec 2016, 3:24 p.m.

Comment on list classification: Discussed with Arianna that this should be green.

Created: 8 Dec 2016, 3:22 p.m.

Comment on list classification: Two family reports for Waisman syndrome (PMID: 25434005; 26399558), plus a third case report (PMID: 27066548) of a French man with early onset parkinsonism with mild mental retardation, a novel nonsense mutation (c.557G>A in exon 2 [p.Trp186stop] of RAB39B) was identified not found in other patients or in Exac. Variants in this gene may be a rare cause of PD, as there are several reports that state it is not a common cause (PMID: 27694831, 27459931).

Created: 3 Nov 2016, 4:04 p.m.