Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome.
Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome.
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DOI：
10.1002/ajmg.a.35979
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发表时间：
2013-07
影响因子：
2
通讯作者：
Percy, Alan K.
中科院分区：
文献类型：
--
作者：
Chapleau, Christopher A.;Lane, Jane;Kirwin, Susan M.;Schanen, Carolyn;Vinette, Kathy M. B.;Stubbolo, Danielle;MacLeod, Patrick;Percy, Alan K.
我们研究的目的是描述MECP2基因的多重突变对一组Rett综合征患者的影响。进一步的分析表明，几乎所有这些都是由顺式突变的从头开始引起的，疾病的严重程度与单一突变无法区分。我们的方法包括招募参与者参加RTT自然历史研究(NHS)。在通过他们的父母或主要照顾者提供知情同意后，对参与者和他们的父母进行了额外的分子评估，以评估每个人中是否存在一个以上的突变和位置。NHS的这些参与者在每次就诊时都要评估临床严重程度。在12名参与者中检测到非连续的MECP2基因变异，在3名参与者中检测到涉及缺失和插入的连续突变。15名参与者中有13人有顺式突变；4人(13人)有3个MECP2突变；2人(15人)同时有顺式和反式突变(即不同的等位基因)。临床严重程度似乎与具有单一类似突变的NHS参与者没有不同。在大多数参与者中发现了顺式基因突变；两个人同时存在顺式基因和反式基因突变。多个突变的存在与更严重的病情无关。然而，如果考虑将基因分配给药物治疗方案，多个突变在未来将需要更多的考虑。
The objective of our study was to characterize the influence of multiple mutations in the MECP2 gene in a cohort of individuals with Rett syndrome. Further analysis demonstrated that nearly all resulted from de novo in cis mutations, where the disease severity was indistinguishable from single mutations. Our methods involved enrolling participants in the RTT Natural History Study (NHS). After providing informed consent through their parents or principal caretakers, additional molecular assessments were performed in the participants and their parents to assess the presence and location of more than one mutation in each. Clinical severity was assessed at each visit in those participants in the NHS. Non-contiguous MECP2 gene variations were detected in 12 participants and contiguous mutations involving a deletion and insertion in three participants. Thirteen of 15 participants had mutations that were in cis; four (of 13) had three MECP2 mutations; two (of 15) had mutations that were both in cis and in trans (i.e. on different alleles). Clinical severity did not appear different from NHS participants with a single similar mutation. Mutations in cis were identified in most participants; two individuals had mutations both in cis and in trans. The presence of multiple mutations was not associated with greater severity. Nevertheless, multiple mutations will require greater thought in the future, if genetic assignment to drug treatment protocols is considered.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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