title: High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability.
abstract: Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.
authors.affiliation: The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Gong
authors.forename: Yu-Wu
authors.initials: YW
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.forename: Yangfei
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xuewu
authors.initials: X
authors.lastname: Gao
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.forename: Zilong
authors.initials: Z
authors.lastname: Qiu
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D018389:Codon, Nonsense; D005786:Gene Expression Regulation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human