Objective: N/A

Background: RAB proteins are small guanosine triphosphatases (GTPases) that are ubiquitous and expressed in all cell types regulating vesicular transport and intracellular membrane trafficking. When expressed in the brain, they exert more specific functions such as neuronal growth and development. Mutations in the RAB39B gene were initially identified in X-linked mental retardation. More recently, two separate families from Australia and Wisconsin were observed to have RAB39B mutations causing early-onset parkinsonism with varying level of intellectual disability in two males. Neuropathologic evaluation found widespread a-synuclein. There is increasing evidence that RAB39B mutations may play a role in archetypal presentation Parkinson’s disease (PD), and herein we report a novel loss-of-function mutation in RAB39B in a female patient with typical early-onset Parkinson’s disease.

Method: N/A

Results: A 41-year-old otherwise healthy female from the Dakotas presented with reduced dexterity in the right upper limb and mixed tremor that worsened over 8 months. She is of British heritage with no family history of PD. Her son has mild intellectual disability and ADHD. On exam, patient exhibited hypomimia, hypokinetic dysarthria with right greater than left bradykinesia and mixed tremor. Her initial MDS-UPDRS score was 40. DaTscan showed reduced radiotracer uptake in the left greater than right putamen; treatment with carbidopa/levodopa conferred excellent response. Genetic testing revealed pathogenic heterozygous mutation Exon 1 c. 188G>A (p.Trp63) in the RAB39B gene.

Conclusion: Mutation of RAB39B may be a very rare cause of typical PD with pathogenesis thought to be due to disruption of a-synuclein homeostasis. Our case reports a novel mutation in the RAB39B gene. Screening of RAB39B mutation should be considered a possibility, although rare, in cases of typical early-onset PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-rab39b-stop-mutation-in-patient-with-typical-early-onset-parkinsons-disease/