Mutations in the transmembrane protein 230 (TMEM230) gene were recently identified in a large Canadian pedigree and 7 smaller Chinese families, nominating TMEM230 as the third gene causing a Mendelian form of late onset Parkinson's disease (PD) with typical Lewy-body pathology (after synuclein alpha (SNCA) and leucine rich repeat kinase 2 (LRRK2)). The protein encoded by TMEM230 remains largely uncharacterized, but initial evidence points to roles in the trafficking of recycling vesicles, retromers, and endosomes, suggesting intriguing links to the pathways targeted by other PD-causing genes. The focus on family-based studies is gaining new momentum in the next-generation sequencing era, for the discovery of further, high-penetrance (medically relevant) genetic variants in PD. However, at this junction, important aspects of the TMEM230 story remain unclear, such as the prevalence of these mutations in the Chinese and other populations of the world, the penetrance of the mutations, and even their mode of inheritance. The first replication studies among Chinese and White PD patients have been largely negative. Furthermore, much more work remains ahead to elucidate the mechanisms by which these mutations might lead to neuronal cell death, alpha-synuclein pathology, and parkinsonism.

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Keywords genetics, mutation, Parkinson's disease, pathogenesis, TMEM230
Persistent URL dx.doi.org/10.1002/mds.27061, hdl.handle.net/1765/108303
Journal Movement Disorders
Citation
Mandemakers, W.J, Quadri, M, Stamelou, M, & Bonifati, V. (2017). TMEM230: How does it fit in the etiology and pathogenesis of Parkinson's disease?. Movement Disorders (Vol. 32, pp. 1159–1162). doi:10.1002/mds.27061