title: Homozygous mutation of VPS16 gene is responsible for an autosomal recessive adolescent-onset primary dystonia.
abstract: Dystonia is a neurological movement disorder that is clinically and genetically heterogeneous. Herein, we report the identification a novel homozygous missense mutation, c.156 C > A in VPS16, co-segregating with disease status in a Chinese consanguineous family with adolescent-onset primary dystonia by whole exome sequencing and homozygosity mapping. To assess the biological role of c.156 C > A homozygous mutation of VPS16, we generated mice with targeted mutation site of Vps16 through CRISPR-Cas9 genome-editing approach. Vps16 c.156 C > A homozygous mutant mice exhibited significantly impaired motor function, suggesting that VPS16 is a new causative gene for adolescent-onset primary dystonia.
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Urology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|BGI Cognitive Genomics Lab, Building No. 11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Collaborative Innovation Center for Cancer Medicine National-Regional Key Technology Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, Shenzhen University 1stAffiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.|The Central Laboratory, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Wenlan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.|The First Clinical College of Anhui Medical University, Hefei 230032, China.
authors.forename: Xiejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Doudou
authors.initials: D
authors.lastname: Zhang
authors.affiliation: BGI Cognitive Genomics Lab, Building No. 11, Beishan Industrial Zone, Yantian District, Shenzhen, Guangdong 518083, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.|The First Clinical College of Anhui Medical University, Hefei 230032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Mali
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The Central Laboratory, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Zongyang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Medicine, Shandong University, 44 West Culture Road, Ji'nan, Shandong 250012, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Luo
authors.affiliation: Collaborative Innovation Center for Cancer Medicine National-Regional Key Technology Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, Shenzhen University 1stAffiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, Guangdong 518035, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D002648:Child; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D000072669:Gene Editing; D005808:Genes, Recessive; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000235:genetics*; D000073359:Exome Sequencing
chemical_list: C424439:VPS16 protein, human; D033921:Vesicular Transport Proteins