Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.
Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.
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克兰费尔特综合征中 X 连锁基因表达失调及其与言语认知的关系。
DOI：
10.1002/ajmg.b.30454
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
DeLisi,LynnE
中科院分区：
文献类型：
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作者：
Vawter,MarquisP;Harvey,PhilipD;DeLisi,LynnE
克氏综合征 (KS) 是一种具有一条或多条额外 X 染色体的染色体核型。 KS 个体经常表现出语言障碍，其表型可能是由于额外 X 染色体上的基因过度表达所致。我们使用 Affymetrix U133P 微阵列平台分析了来自具有 KS 记录的男性和对照男性的淋巴母细胞系的 mRNA。经过Benjamini-Hochberg错误发现调整后，KS组与对照组相比有129个差异表达基因（DEG）。 DEG 包括 14 个 X 染色体基因，这些基因明显过多。 Y 染色体的 DEG 为零。在基因表达-认知关系的探索性分析中，12 个 DEG 显示表达与 KS 中言语认知测量显着相关。一种假常染色体基因 GTPBP6（GTP 结合蛋白 6，推定）的过度表达与言语智商（r = −0.86，P< 0.001）和其他四种言语能力指标呈负相关。与 XY 对照相比，在 KS 中发现 XIST 过度表达，这表明 X 染色体上的许多基因沉默可能发生在 KS 中，类似于 XX 女性。八个 DEG 的微阵列结果通过定量 PCR 进行了验证。在之前比较女性和男性大脑的研究中，14 X 染色体 DEG 没有差异表达，这表明 KS 特有的失调特征。对显示言语认知与基因表达相关性的 X 连锁 DEG（例如 GTPBP6、TAF9L 和 CXORF21）的检查可能会在这些基因、神经发育和语言功能之间建立因果关系。候选基因的筛选可以作为 KS 早期诊断的生物标志物。 © 2007 Wiley-Liss, Inc.
Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini–Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over‐represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression–cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene,GTPBP6(GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = −0.86,P< 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X‐linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition–gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. © 2007 Wiley‐Liss, Inc.