Parkinson Disease and Complex Parkinsonism
Gene: RAB39B
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
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.
Phenotypes for gene: RAB39B were changed from ?Waisman syndrome; early-onset parkinsonism and intellectual disability to Waisman syndrome, OMIM:311510; early-onset parkinsonism and intellectual disability
19th Dec 2016: panel revised according to expert review and further curation.
This gene has been classified as Green List (High Evidence).
Phenotypes for RAB39B were set to ?Waisman syndrome;early-onset parkinsonism and intellectual disability
Mode of inheritance for RAB39B was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
This gene has been classified as Green List (High Evidence).
Publications for RAB39B were set to 25434005;26399558;27694831;27459931;27066548;2639955
Mode of inheritance for RAB39B was changed to X-LINKED: hemizygous mutation in males, biallelic mutations in females
This gene has been classified as Amber List (Moderate Evidence).
Phenotypes for RAB39B were set to ?Waisman syndrome
This gene has been classified as Red List (Low Evidence).
RAB39B was created by ellenmcdonagh
RAB39B was added to Parkinson Disease and Complex Parkinsonismpanel. Sources: Expert