High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability.
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 largel...
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doaj-070aaf91bfd74cc3addfa9d6ddbc4ed62020-11-25T02:03:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3473910.1371/journal.pone.0034739High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability.Xiaohong GongYu-Wu JiangXin ZhangYu AnJun ZhangYe WuJingmin WangYangfei SunYanyan LiuXuewu GaoYiping ShenXiru WuZilong QiuLi JinBai-Lin WuHongyan WangIntellectual 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.http://europepmc.org/articles/PMC3324537?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaohong Gong Yu-Wu Jiang Xin Zhang Yu An Jun Zhang Ye Wu Jingmin Wang Yangfei Sun Yanyan Liu Xuewu Gao Yiping Shen Xiru Wu Zilong Qiu Li Jin Bai-Lin Wu Hongyan Wang |
spellingShingle |
Xiaohong Gong Yu-Wu Jiang Xin Zhang Yu An Jun Zhang Ye Wu Jingmin Wang Yangfei Sun Yanyan Liu Xuewu Gao Yiping Shen Xiru Wu Zilong Qiu Li Jin Bai-Lin Wu Hongyan Wang High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PLoS ONE |
author_facet |
Xiaohong Gong Yu-Wu Jiang Xin Zhang Yu An Jun Zhang Ye Wu Jingmin Wang Yangfei Sun Yanyan Liu Xuewu Gao Yiping Shen Xiru Wu Zilong Qiu Li Jin Bai-Lin Wu Hongyan Wang |
author_sort |
Xiaohong Gong |
title |
High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. |
title_short |
High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. |
title_full |
High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. |
title_fullStr |
High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. |
title_full_unstemmed |
High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. |
title_sort |
high proportion of 22q13 deletions and shank3 mutations in chinese patients with intellectual disability. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3324537?pdf=render |
work_keys_str_mv |
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