Evidence for Three Subgroups of Female FMR1 Premutation Carriers Defined by Distinct Neuropsychiatric Features: A Pilot Study.
Evidence for Three Subgroups of Female FMR1 Premutation Carriers Defined by Distinct Neuropsychiatric Features: A Pilot Study.
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DOI：
10.3389/fnint.2021.797546
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发表时间：
2021
影响因子：
3.5
通讯作者：
Erickson CA
中科院分区：
文献类型：
--
作者：
Schmitt LM;Dominick KC;Liu R;Pedapati EV;Ethridge LE;Smith E;Sweeney JA;Erickson CA
脆性X智力低下1(FMR1)基因5‘非翻译区超过200个胞嘧啶-鸟嘌呤-鸟嘌呤(CGG)三核苷酸重复会导致“全突变”，即临床上的脆性X综合征(FXS)，而55-200个重复会导致“前突变”。FMR1前突变携带者(PMC)患一系列精神、神经认知和身体疾病的风险增加。很少有研究考察女性PMC中神经精神特征的不同表达，以及女性PMC之间的不同表现是否反映了独特亚群中特征的不同表现。在目前的初步研究中，我们检查了41名女性PMC(年龄17-78岁)和15名年龄、性别和智商匹配的典型发育对照(TDC)，通过一系列自我报告、眼球跟踪、表达语言、神经认知和静息状态EEG测量来确定识别离散簇的可行性。其次，我们试图确定区分这些女性私营军事公司集群的关键特征。我们找到了一个使用k-均值聚类的三聚类解决方案。第一组代表精神疾病特征组(占我们样本的27%)；第二组代表执行功能障碍和高频神经振荡活动增加的组(32%)；第三组代表相对未受影响的组(41%)。我们的发现表明，使用数据驱动的方法来使用多方法评估组合来识别女性PMC中自然出现的簇是可行的。CGG重复计数及其与神经精神病学特征的关联因集群而异。总之，我们的发现为每个女性PMC集群潜在的不同病理生理机制和风险因素提供了重要的见解，最终可能有助于为治疗方案提供新的和个性化的靶点。
Over 200 Cytosine-guanine-guanine (CGG) trinucleotide repeats in the 5′ untranslated region of the Fragile X mental retardation 1 (FMR1) gene results in a “full mutation,” clinically Fragile X Syndrome (FXS), whereas 55 – 200 repeats result in a “premutation.” FMR1 premutation carriers (PMC) are at an increased risk for a range of psychiatric, neurocognitive, and physical conditions. Few studies have examined the variable expression of neuropsychiatric features in female PMCs, and whether heterogeneous presentation among female PMCs may reflect differential presentation of features in unique subgroups. In the current pilot study, we examined 41 female PMCs (ages 17–78 years) and 15 age-, sex-, and IQ-matched typically developing controls (TDC) across a battery of self-report, eye tracking, expressive language, neurocognitive, and resting state EEG measures to determine the feasibility of identifying discrete clusters. Secondly, we sought to identify the key features that distinguished these clusters of female PMCs. We found a three cluster solution using k-means clustering. Cluster 1 represented a psychiatric feature group (27% of our sample); cluster 2 represented a group with executive dysfunction and elevated high frequency neural oscillatory activity (32%); and cluster 3 represented a relatively unaffected group (41%). Our findings indicate the feasibility of using a data-driven approach to identify naturally occurring clusters in female PMCs using a multi-method assessment battery. CGG repeat count and its association with neuropsychiatric features differ across clusters. Together, our findings provide important insight into potential diverging pathophysiological mechanisms and risk factors for each female PMC cluster, which may ultimately help provide novel and individualized targets for treatment options.
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影响因子：
2.9
作者：
Goodrich-Hunsaker, Naomi J;Wong, Ling M;Simon, Tony J
通讯作者：
Simon, Tony J
影响因子：
3
作者：
Alvarez-Mora, Maria Isabel;Rodriguez-Revenga, Laia;Mila, Montserrat
通讯作者：
Mila, Montserrat
DOI：
10.1212/nxg.0000000000000045
发表时间：
2016-02
期刊：
Neurology. Genetics
影响因子：
--
作者：
Hall DA;Robertson-Dick EE;O'Keefe JA;Hadd AG;Zhou L;Berry-Kravis E
通讯作者：
Berry-Kravis E
影响因子：
6.1
作者：
Goswami, Sonal;Cavalier, Sheridan;Gibson, Jay R.
通讯作者：
Gibson, Jay R.
影响因子：
3.7
作者：
Hartley SL;Seltzer MM;Hong J;Greenberg JS;Smith L;Almeida D;Coe C;Abbeduto L
通讯作者：
Abbeduto L