FMRP Levels in Human Peripheral Blood Leukocytes Correlates with Intellectual Disability.
FMRP Levels in Human Peripheral Blood Leukocytes Correlates with Intellectual Disability.
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人外周血白细胞中的FMRP水平与智力障碍相关。
DOI：
10.3390/diagnostics11101780
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发表时间：
2021-09-28
期刊：
影响因子：
--
通讯作者：
Tassone F
中科院分区：
文献类型：
--
作者：
Roth M;Ronco L;Cadavid D;Durbin-Johnson B;Hagerman RJ;Tassone F
脆性X综合征（FXS）是遗传性智力残疾的最常见形式。FXS是一种X连锁神经发育障碍，由脆性X智力低下基因FMR 1的5′非翻译区（UTR）中的CGG三核苷酸重复扩增引起。大于200个CGG重复导致基因的表观遗传沉默，导致脆性X智力低下蛋白（FMRP）的缺乏或缺失。FMRP的丢失被认为是FXS的根本原因。外周血单个核细胞（PBMC）中FMRP表达与神经功能之间的关系尚未得到很好的确定。已经描述了检测和测量FMR 1和FMRP的测定法;然而，没有一种测定法足够灵敏、精确或定量以适当地表征认知能力与在PBMC中测量的CGG重复数、FMR 1 mRNA表达或FMRP表达之间的关系。为了解决这些局限性，开发和优化了两种新的免疫测定，电化学发光免疫测定和多参数流式细胞术测定。这两种试验均在从27名研究参与者中分离的PMBC上进行，FMR 1 CGG重复范围从正常到完全突变。校正甲基化后，观察到CGG重复数与FMR 1 mRNA表达水平之间呈显着正相关，而FMRP水平与CGG重复扩增之间呈显着负相关。重要的是，在PBMC中测量的智商（IQ）和FMRP表达之间观察到高度正相关。
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is an X-linked, neurodevelopmental disorder caused by a CGG trinucleotide repeat expansion in the 5′ untranslated region (UTR) of the Fragile X Mental Retardation gene, FMR1. Greater than 200 CGG repeats results in epigenetic silencing of the gene leading to the deficiency or absence of Fragile X mental retardation protein (FMRP). The loss of FMRP is considered the root cause of FXS. The relationship between neurological function and FMRP expression in peripheral blood mononuclear cells (PBMCs) has not been well established. Assays to detect and measure FMR1 and FMRP have been described; however, none are sufficiently sensitive, precise, or quantitative to properly characterize the relationships between cognitive ability and CGG repeat number, FMR1 mRNA expression, or FMRP expression measured in PBMCs. To address these limitations, two novel immunoassays were developed and optimized, an electro-chemiluminescence immunoassay and a multiparameter flow cytometry assay. Both assays were performed on PMBCs isolated from 27 study participants with FMR1 CGG repeats ranging from normal to full mutation. After correcting for methylation, a significant positive correlation between CGG repeat number and FMR1 mRNA expression levels and a significant negative correlation between FMRP levels and CGG repeat expansion was observed. Importantly, a high positive correlation was observed between intellectual quotient (IQ) and FMRP expression measured in PBMCs.
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DOI：
10.1016/j.tig.2017.07.008
发表时间：
2017-10
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Davis JK;Broadie K
通讯作者：
Broadie K
影响因子：
5.1
作者：
Jiraanont P;Kumar M;Tang HT;Espinal G;Hagerman PJ;Hagerman RJ;Chutabhakdikul N;Tassone F
通讯作者：
Tassone F
脆弱X综合征中的基因，大脑和行为关系：来自神经影像研究的证据。
影响因子：
--
作者：
Lightbody, Amy A.;Reiss, Allan L.
通讯作者：
Reiss, Allan L.
影响因子：
3.4
作者：
Graef, John D.;Wu, Hao;Wallace, Owen
通讯作者：
Wallace, Owen
影响因子：
30.8
作者：
HINDS, HL;ASHLEY, CT;SCHALLING, M
通讯作者：
SCHALLING, M