Mutation in the SYNJ1 Gene Associated with Autosomal Recessive, Early-Onset Parkinsonism (pages 1208–1215)
Marialuisa Quadri, Mingyan Fang, Marina Picillo, Simone Olgiati, Guido J. Breedveld, Josja Graafland, Bin Wu, Fengping Xu, Roberto Erro, Marianna Amboni, Sabina Pappatà, Mario Quarantelli, Grazia Annesi, Aldo Quattrone, Hsin F. Chien, Egberto R. Barbosa, The International Parkinsonism Genetics Network, Ben A. Oostra, Paolo Barone, Jun Wang and Vincenzo Bonifati
Version of Record online: 6 AUG 2013 | DOI: 10.1002/humu.22373
By homozygosity mapping and exome sequencing in an Italian consanguineous family with early-onset Parkinsonism, we identified a disease-segregating homozygous SYNJ1 mutation.
SYNJ1 encodes synaptojanin 1, a phosphoinositide phosphatase, essential for the post-endocytic recycling of synaptic vesicles. This work delineates a novel form of Mendelian Parkinsonism and provides further evidence for abnormal synaptic vesicle recycling as a central theme in the pathogenesis. We also provide a detailed description of the clinical phenotype, and structural and functional neuroimaging of this novel form.