Size and methylation mosaicism in males with Fragile X syndrome.
Size and methylation mosaicism in males with Fragile X syndrome.
复制标题
DOI：
10.1080/14737159.2017.1377612
复制
发表时间：
2017-11
影响因子：
5.1
通讯作者：
Tassone F
中科院分区：
文献类型：
--
作者：
Jiraanont P;Kumar M;Tang HT;Espinal G;Hagerman PJ;Hagerman RJ;Chutabhakdikul N;Tassone F
大小和甲基化镶嵌是脆性X综合征（FXS）的常见现象。在这里，作者报告了一项对12名患有非典型嵌合体的脆弱X型男性的研究，其中7人表现出自闭症谱系障碍。采用Southern Blot和PCR联合分析CGG等位基因的大小和甲基化。分别采用qRT-PCR和均匀时间分辨荧光法检测FMR1 mRNA和FMRP的表达。DNA分析显示非典型的大小或甲基化嵌合体，具有完全突变和较小的（正常到预突变）等位基因，以及甲基化和未甲基化等位基因的组合。4个个体携带CGG重复序列和部分侧翼区域的缺失。参与者的甲基化程度反映在这些受试者中检测到的较低的FMR1 mRNA和FMRP表达水平上。基因表达减少可能是导致这些受试者出现认知障碍的主要原因；尽管正常等位基因的存在似乎不能弥补完全突变的存在，但在一些（但不是所有）报道的病例中，它与更好的认知功能相关，这强调了FXS分子和临床特征的复杂性。
Size and methylation mosaicism are a common phenomenon in Fragile X syndrome (FXS). Here, the authors report a study on twelve fragile X males with atypical mosaicism, seven of whom presented with autism spectrum disorder. A combination of Southern Blot and PCR analysis was used for CGG allele sizing and methylation. FMR1 mRNA and FMRP expression were measured by qRT-PCR and by Homogeneous Time Resolved Fluorescence methodology, respectively. DNA analysis showed atypical size- or methylation-mosaicism with both, full mutation and smaller (normal to premutation) alleles, as well as a combination of methylated and unmethylated alleles. Four individuals carried a deletion of the CGG repeat and portions of the flanking regions. The extent of methylation among the participants was reflected in the lower FMR1 mRNA and FMRP expression levels detected in these subjects. Decreased gene expression is likely the main contributor to the cognitive impairment observed in these subjects; although the presence of a normal allele did not appear to compensate for the presence of the full mutation, it correlated with better cognitive function in some but not all of the reported cases emphasizing the complexity of the molecular and clinical profile in FXS.
登录
查看更多内容
影响因子：
2.6
作者：
Allen, EG;Sherman, S;Letz, R
通讯作者：
Letz, R
影响因子：
5.3
作者：
Edamura, KN;Pearson, CE
通讯作者：
Pearson, CE
影响因子：
3.7
作者：
Brouwer, J. R.;Mientjes, E. J.;Willemsen, R.
通讯作者：
Willemsen, R.
影响因子：
14.9
作者：
Genç, B;Müller-Hartmann, H;Doerfler, W
通讯作者：
Doerfler, W
DOI：
10.1002/ajmg.1320430134
发表时间：
1992-04-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
DEVYS, D;BIANCALANA, V;OBERLE, I
通讯作者：
OBERLE, I