title: Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation.
abstract: The molecular basis of autosomal dominant microcephaly, a disorder associated with small head circumferences that results in variable mental retardation, is largely unknown. In the present study, we conducted a variation analysis of the DPP6 gene in patients with autosomal dominant microcephaly and variable mental retardation. The copy number variation analysis of DPP6 was performed on DNA samples from 22 patients with microcephaly using high-resolution, array-based genomic hybridization, and sequence analysis was performed to screen mutations in another 50 microcephalic patients. Two de novo deletions and one missense mutation in familial microcephalic patients were identified. The transfection of plasmids encoding green fluorescent protein-pLLU2G-shDPP6 fusion proteins in mouse brains revealed that the decreased expression of the DPP6 gene slightly reduced the weight of the mouse brains and resulted in mouse learning disabilities compared with their wild-type littermates. Our data indicate that the loss-of-function variations in DPP6 are associated with autosomal dominant microcephaly and mental retardation. DPP6 appears to play a major role in the regulation of proliferation and migration of neurons in neurogenesis, most likely by participating in neuronal electrical excitability, synaptic integration, and plasticity.
authors.affiliation: Department of Medical Genetics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical College, Guangzhou, China; Department of Molecular Biology, Guangzhou Medical College, Guangzhou, China. Electronic address: canliao@hotmail.com.
authors.forename: Can
authors.initials: C
authors.lastname: Liao
authors.forename: Fang
authors.initials: F
authors.lastname: Fu
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Yang
authors.forename: Hua-Yi
authors.initials: HY
authors.lastname: Liao
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Yan
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Dong-Zhi
authors.initials: DZ
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D051379:Mice; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C503535:DPP6 protein, human; C569992:DPP6 protein, mouse; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
keywords: Array-CGH; Autosomal dominant microcephaly; DPP6 gene; Mental retardation