title: AMPD1 functional variants associated with autism in Han Chinese population.
abstract: Autism is a childhood neurodevelopmental disorder with high heterogeneity. Following our genome-wide associated loci with autism, we performed sequencing analysis of the coding regions, UTR and flanking splice junctions of AMPD1 in 830 Chinese autism individuals as well as 514 unrelated normal controls. Fourteen novel variants in the coding sequence were identified, including 11 missense variants and 3 synonymous mutations. Among these missense variants, 10 variants were absent in 514 control subjects, and conservative and functional prediction was carried out. Mitochondria activity and lactate dehydrogenase assay were performed in 5 patients' lymphoblast cell lines; p.P572S and p.S626C showed decreased mitochondrial complex I activity, and p.S626C increased lactate dehydrogenase release in medium. Conclusively, our data suggested that mutational variants in AMPD1 contribute to autism risk in Han Chinese population, uncovering the contribution of mutant protein to disease development that operates via mitochondria dysfunction and cell necrosis.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110, Xiangya Road, Changsha, Hunan, China.
authors.forename: Lusi
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ou
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Pan
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.forename: Tianyun
authors.initials: T
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zou
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D000659:AMP Deaminase / Q000235:genetics*; D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics
chemical_list: D007770:L-Lactate Dehydrogenase; D000659:AMP Deaminase; C514117:AMPD1 protein, human