Correlation between FMR1 expression and clinical phenotype in discordant dichorionic–diamniotic monozygotic twin sisters with the fragile x mutation
Correlation between FMR1 expression and clinical phenotype in discordant dichorionic–diamniotic monozygotic twin sisters with the fragile x mutation
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具有脆性x突变的不一致双绒毛膜-双羊膜同卵双胞胎姐妹中FMR1表达与临床表型的相关性
DOI：
10.1136/jmedgenet-2013-101978
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发表时间：
2013
影响因子：
4
通讯作者：
R. Duan
中科院分区：
文献类型：
--
作者：
Wen Huang;S. Luo;J. Ou;F. Zhu;Yan Xia;J. Xue;Q. Pan;Lingqian Wu;R. Duan
背景脆性X染色体完全突变女性患者的临床表型差异很大。不一致的单卵双胞胎的比较提供了机会，以确定影响疾病表型遗传率的关键因素。目的探讨影响脆性X综合征（FXS）表型表达的关键因素。方法和结果我们描述了一对不和谐的单卵双胞胎女性（双卵双胞胎，二，二）与全突变。在一系列神经心理学测试中，对他们在身体、精神和行为特征方面的表型不一致程度进行了量化，这些测试差异很大。他们的FMR 1表达水平和血液中的全基因组DNA甲基化谱相似。他们相似的生活经历也表明环境因素的影响有限。然而，双胞胎A的发根中正常X染色体的偏斜失活，导致FMR 1表达与双胞胎B相比大幅减少，可以充分解释其广泛变异的表型。结论毛根FMR 1表达水平的6倍变异反映了FMRP（fragile X mental retardation protein，脆性X智力低下蛋白）在脑内的表达水平，是双胞胎智商、认知和社会能力表型差异的原因。此外，考虑到Di-Di型孪生和不同的CGG重复序列大小，CGG扩增应在妊娠第3天分裂前发生。
Background The clinical phenotypes of females with fragile X full mutations vary drastically. Comparisons of discordant monozygotic twins provide opportunities to ascertain crucial factors that influence disease phenotype penetrance. Objective To identify crucial factors influencing the phenotypic expression of fragile X syndrome (FXS). Methods and results We describe a pair of discordant monozygotic female twins (dichorionic–diamniotic, Di–Di) with full mutation. The degrees of their phenotypic discordance regarding physical, psychiatric and behavioural features were quantified in a series of neuropsychological tests that varied significantly. Their FMR1 expression levels and whole genome DNA methylation profiling in blood were similar. Their similar life experiences also suggested that environmental factors had limited influence. However, the skewed inactivation of the normal X chromosome in the hair roots of twin A, resulting in large reduction in FMR1 expression compared to that of twin B, could adequately explain their widely variable phenotypes. Conclusions The sixfold variation in hair root FMR1 expression, which reflected FMRP (fragile X mental retardation protein) expression in the brain, accounted for the disparate phenotypes in IQ, cognition, and social capability between the twins. Additionally, considering the Di–Di type twinning and different CGG repeat sizes, CGG expansion should occur before splitting at day 3 of gestation.
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影响因子：
4.8
作者：
Pomraning, Kyle R.;Smith, Kristina M.;Freitag, Michael
通讯作者：
Freitag, Michael
FMR1 CGG 重复序列的家族遗传。
影响因子：
9.8
作者：
Nolin,SL;Lewis3rd,FA;Ye,LL;HouckJr,GE;Glicksman,AE;Limprasert,P;Li,SY;Zhong,N;Ashley,AE;Feingold,E;Sherman,SL;Brown,WT
通讯作者：
Brown,WT
关于脆弱X综合征生物学的新观点。
影响因子：
4
作者：
Wang, Tao;Bray, Steven M.;Warren, Stephen T.
通讯作者：
Warren, Stephen T.
影响因子：
158.5
作者：
Wilcox, AJ;Baird, DD;Wenberg, CR
通讯作者：
Wenberg, CR