Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation.
Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation.
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患有 MECP2 新突变的 47,XXX 患者的 Rett 综合征。
DOI：
10.1002/ajmg.a.20320
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Schanen,NCarolyn
中科院分区：
文献类型：
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作者：
Hammer,Sara;Dorrani,Naghmeh;Hartiala,Jaana;Stein,Stuart;Schanen,NCarolyn
Rett综合征是由MECP2基因突变引起的，MECP2基因位于Xq28上，可被X失活。MECP2编码甲基CpG结合蛋白2，这是一种广泛表达的甲基化DNA转录抑制因子。MECP2中的突变主要是男性生殖系中的从头事件，因此导致过多的受影响的女性。在这里，我们报告了一个独特的47，XXX女孩，患有相对轻微的非典型Rett综合征，最初导致回归诊断为婴儿自闭症。对MECP2基因进行突变分析，发现一个新的MECP2突变L100V。对一组X连锁微卫星标记的检查表明，她额外的X染色体是母系遗传的。通过分析雄激素受体基因的甲基化，确定了X失活模式，表明她父亲的等位基因优先失活。无法确定hMECP2突变的父母来源，因为她对其突变两侧的内含子多态缺乏信息。这是第一例报告的女性性染色体三体和MECP2突变，它说明了等位基因剂量对Rett综合征表型严重程度的重要性。©2003 Wiley-Liss公司
Rett syndrome is caused by mutation inMECP2, a gene located on Xq28 and subject to X‐inactivation.MECP2encodes methyl CpG‐binding protein 2, a widely expressed transcriptional repressor of methylated DNA. Mutations inMECP2are primarily de novo events in the male germ line and thus lead to an excess of affected females. Here we report the identification of a unique 47,XXX girl with relatively mild atypical Rett syndrome leading initially to a diagnosis of infantile autism with regression. Mutation analysis of theMECP2gene identified a de novoMECP2mutation, L100V. Examination of a panel of X‐linked microsatellite markers indicated that her supernumerary X chromosome is maternally derived. X‐inactivation patterns were determined by analysis of methylation of the androgen receptor locus, and indicated preferential inactivation of her paternal allele. The parental origin of herMECP2mutation could not be determined because she was uninformative for intronic polymorphisms flanking her mutation. This is the first reported case of sex chromosome trisomy andMECP2mutation in a female, and it illustrates the importance of allele dosage on the severity of Rett syndrome phenotype. © 2003 Wiley‐Liss, Inc.