• 文章类型: Journal Article
    目前强迫症的心理治疗方法,虽然有效,有复杂的结果和混合的疗效。先前的研究已经观察到强迫症患者的基线脑激活模式,阐明这种疾病的一些含义。观察基于证据的精神疗法对强迫症脑激活的影响(通过MRI)可以提供更全面的病理学概述。这项系统评价和荟萃分析评估了认知行为疗法(CBT)与暴露反应预防(ERP)对强迫症患者脑激活的影响。系统地搜索了学术数据库,评估的结局包括基线和治疗后大脑激活和症状严重程度的变化.患者(n=193)已确认OCD诊断,并接受了由训练有素的治疗师提供的ERP计划的原型CBT。CBT与ERP计划的参与者表现出症状严重程度的显着改善(Cohen'sd=-1.91)。总的来说,CBT与ERP导致额叶治疗后活化降低(Cohen'sd=0.40),顶叶(科恩的d=0.79),时间(科恩的d=1.02),和枕叶(科恩的d=0.76),和小脑(科恩的d=-0.78)。研究结果支持CBT与ERP改善OCD患者脑激活异常的能力。通过识别提高激活水平的区域,心理治疗计划可能受益于功能特异性功能的增加,这些功能特异性功能可以改善治疗结果.
    Current psychotherapeutic treatments for OCD, while effective, have complex outcomes with mixed efficacy. Previous research has observed baseline brain activation patterns in OCD patients, elucidating some of the implications of this disorder. Observing the effects of evidence-based psychotherapeutics for OCD on brain activation (through MRI) may provide a more comprehensive outline of pathology. This systematic review and meta-analysis evaluated the effects of cognitive behavioural therapy (CBT) with exposure-response prevention (ERP) on brain activation in OCD patients. Academic databases were systematically searched, and the outcomes evaluated included changes in brain activation and symptom severity between baseline and post-treatment. Patients (n = 193) had confirmed OCD diagnosis and underwent protocolized CBT with ERP programs delivered by trained therapists. Participants in the CBT with ERP programs demonstrated significant improvements in symptom severity (Cohen\'s d = - 1.91). In general, CBT with ERP resulted in decreased activation post-treatment in the frontal (Cohen\'s d = 0.40), parietal (Cohen\'s d = 0.79), temporal (Cohen\'s d = 1.02), and occipital lobe (Cohen\'s d = 0.76), and cerebellum (Cohen\'s d = - 0.78). The findings support CBT with ERP\'s ability to improve brain activation abnormalities in OCD patients. By identifying regions that improved activation levels, psychotherapy programs may benefit from the addition of function-specific features that could improve treatment outcomes.
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  • 文章类型: Journal Article
    快速眼动睡眠行为障碍(RBD)的神经影像学研究可以提供有关帕金森病(PD)发病机理的基本问题。跨模式,功能磁共振成像(fMRI)可能更适合识别路易体疾病早期阶段的神经网络之间的变化,当结构变化可能是微妙的或不存在时。这篇综述综合了RBD的所有fMRI研究结果,以进一步了解路易体疾病的病理生理学和进展。根据PRISMA指南在2000年1月至2024年2月之间进行的系统评价,确定了总共32项研究,用于孤立性RBD(iRBD)或继发于PD的RBD患者的原始fMRI研究。与健康对照相比,iRBD患者在脑干核中可检测到常见的功能改变,基底神经节,额叶和枕叶,和整个大脑网络测量。已确诊的PD和RBD患者表现出整个大脑和脑干核的功能连接下降,但与没有RBD的PD患者相比,小脑和额叶的功能连接增加。最后,静息状态功能连接的纵向变化与疾病进展有关.目前,RBD中的fMRI研究已经证明了运动和非运动途径中神经变性的早期特征。虽然需要更多的工作,这些发现有可能让我们了解疾病,有助于区分前驱PD和路易体前驱痴呆,并支持在未来的疾病改良试验中开发基于功能磁共振成像的表型转化和进展结局指标。©2024作者(S)。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
    Neuroimaging studies in rapid eye movement sleep behavior disorder (RBD) can inform fundamental questions about the pathogenesis of Parkinson\'s disease (PD). Across modalities, functional magnetic resonance imaging (fMRI) may be better suited to identify changes between neural networks in the earliest stages of Lewy body diseases when structural changes may be subtle or absent. This review synthesizes the findings from all fMRI studies of RBD to gain further insight into the pathophysiology and progression of Lewy body diseases. A total of 32 studies were identified using a systematic review conducted according to PRISMA guidelines between January 2000 to February 2024 for original fMRI studies in patients with either isolated RBD (iRBD) or RBD secondary to PD. Common functional alterations were detectable in iRBD patients compared with healthy controls across brainstem nuclei, basal ganglia, frontal and occipital lobes, and whole brain network measures. Patients with established PD and RBD demonstrated decreased functional connectivity across the whole brain and brainstem nuclei, but increased functional connectivity in the cerebellum and frontal lobe compared with those PD patients without RBD. Finally, longitudinal changes in resting state functional connectivity were found to track with disease progression. Currently, fMRI studies in RBD have demonstrated early signatures of neurodegeneration across both motor and non-motor pathways. Although more work is needed, such findings have the potential to inform our understanding of disease, help to distinguish between prodromal PD and prodromal dementia with Lewy bodies, and support the development of fMRI-based outcome measures of phenoconversion and progression in future disease modifying trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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  • 文章类型: Journal Article
    在更生态有效的条件下对步态及其神经元相关性的研究以及实时反馈可视化在神经运动康复研究中变得越来越重要。步态实时分析互动实验室(GRAIL)通过身临其境的虚拟现实创建更自然但受控的环境,为步态和步态相关的研究提供了先进的机会。研究步态的神经元方面需要并行记录大脑活动,例如通过移动脑电图(EEG)和/或移动功能近红外光谱(fNIRS),必须与行走时记录的动力学和/或运动学数据同步。此概念验证研究概述了使用实验室流层(LSL)生态系统进行实时、两个独立操作的多通道EEG和fNIRS测量设备和步态动力学的同时数据收集。在这种情况下,描述了使用光电二极管来同步系统的定制方法。这项研究证明了GRAIL中神经生理学,运动学和动力学数据收集的同步数据采集的可实现的时间准确性。通过在开始任务和棋盘测试中使用事件相关的脑血流动力学活动和视觉诱发电位,我们能够确认我们的测量系统可以复制已知的生理现象,潜伏期在毫秒范围内,并以足够的精度将神经生理学和动力学数据相互关联。
    The investigation of gait and its neuronal correlates under more ecologically valid conditions as well as real-time feedback visualization is becoming increasingly important in neuro-motor rehabilitation research. The Gait Real-time Analysis Interactive Lab (GRAIL) offers advanced opportunities for gait and gait-related research by creating more naturalistic yet controlled environments through immersive virtual reality. Investigating the neuronal aspects of gait requires parallel recording of brain activity, such as through mobile electroencephalography (EEG) and/or mobile functional near-infrared spectroscopy (fNIRS), which must be synchronized with the kinetic and /or kinematic data recorded while walking. This proof-of-concept study outlines the required setup by use of the lab streaming layer (LSL) ecosystem for real-time, simultaneous data collection of two independently operating multi-channel EEG and fNIRS measurement devices and gait kinetics. In this context, a customized approach using a photodiode to synchronize the systems is described. This study demonstrates the achievable temporal accuracy of synchronous data acquisition of neurophysiological and kinematic and kinetic data collection in the GRAIL. By using event-related cerebral hemodynamic activity and visually evoked potentials during a start-to-go task and a checkerboard test, we were able to confirm that our measurement system can replicate known physiological phenomena with latencies in the millisecond range and relate neurophysiological and kinetic data to each other with sufficient accuracy.
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  • 文章类型: Journal Article
    通过基准标记对头部姿势的光学跟踪已经被证明能够在磁共振成像期间有效地校正大脑中的运动伪影,但是由于冗长的校准和设置时间而仍然难以在临床中实现。由于运动校正所需的亚毫米空间分辨率,用于无标记头部姿势估计的深度学习的进展尚未应用于该问题。在目前的工作中,描述了两个用于开发和训练神经网络的光学跟踪系统:一个基于标记的系统(用于测量地面真相头部姿势的测试平台)具有高跟踪保真度作为训练标签,和一个无标记的基于深度学习的系统,使用无标记的头部的图像作为网络的输入。无标记系统有可能克服标记物遮挡的问题,标记的刚性连接不足,冗长的校准时间,以及跨自由度(DOF)的不平等性能,所有这些都阻碍了在临床中采用基于标记的解决方案。提供了有关用作地面实况的自定义莫尔增强基准标记的开发以及两个光学跟踪系统的校准程序的详细信息。此外,描述了合成头部姿态数据集的开发,以证明简单卷积神经网络的概念和初始预训练。结果表明,地面实况系统已得到充分校准,可以跟踪磁头姿态,误差<1mm和<1°。跟踪健康的数据,成人参与者显示。预训练结果表明,在训练数据集包含和排除的头部模型上,6个自由度的平均均方根误差为0.13和0.36(mm或度)。分别。总的来说,这项工作表明了基于深度学习的方法的出色可行性,并将使未来的工作能够在MRI环境中对真实数据集进行培训和测试。
    Optical tracking of head pose via fiducial markers has been proven to enable effective correction of motion artifacts in the brain during magnetic resonance imaging but remains difficult to implement in the clinic due to lengthy calibration and set up times. Advances in deep learning for markerless head pose estimation have yet to be applied to this problem because of the sub-millimetre spatial resolution required for motion correction. In the present work, two optical tracking systems are described for the development and training of a neural network: one marker-based system (a testing platform for measuring ground truth head pose) with high tracking fidelity to act as the training labels, and one markerless deep-learning-based system using images of the markerless head as input to the network. The markerless system has the potential to overcome issues of marker occlusion, insufficient rigid attachment of the marker, lengthy calibration times, and unequal performance across degrees of freedom (DOF), all of which hamper the adoption of marker-based solutions in the clinic. Detail is provided on the development of a custom moiré-enhanced fiducial marker for use as ground truth and on the calibration procedure for both optical tracking systems. Additionally, the development of a synthetic head pose dataset is described for the proof of concept and initial pre-training of a simple convolutional neural network. Results indicate that the ground truth system has been sufficiently calibrated and can track head pose with an error of <1 mm and <1°. Tracking data of a healthy, adult participant are shown. Pre-training results show that the average root-mean-squared error across the 6 DOF is 0.13 and 0.36 (mm or degrees) on a head model included and excluded from the training dataset, respectively. Overall, this work indicates excellent feasibility of the deep-learning-based approach and will enable future work in training and testing on a real dataset in the MRI environment.
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  • 文章类型: Journal Article
    COVID-19大流行引起了人们对该病毒长期后果的关注,特别是以长期COVID为特征的持续症状。这种综合症,在初次感染后可以持续数月,包括一系列对大脑健康和痴呆症研究有重大影响的神经和神经精神表现。这篇综述探讨了当前对长COVID认知的理解,神经学,精神症状及其对大脑刺激和神经影像学研究的潜在影响。它认为,研究人员必须调整他们的研究设计和筛选过程,以解决长COVID的混杂影响,并确保他们的研究结果的准确性和可靠性。为了加深对这种情况及其对大脑健康的长期影响的理解,检讨提出一系列策略,包括开发标准化的筛查工具,对潜在机制的调查,危险因素和保护因素的识别。它还强调了合作研究工作和国际数据共享平台在加快发现和开发针对长期COVID个体的有针对性干预措施方面的重要性。随着这种情况的流行,神经科学界必须齐心协力应对这一挑战,并为长期COVID患者提供支持。
    The COVID-19 pandemic has brought attention to the long-term consequences of the virus, particularly the persistent symptoms that characterize long COVID. This syndrome, which can last for months after the initial infection, includes a range of neurological and neuropsychiatric manifestations that have significant implications for brain health and dementia research. This review explores the current understanding of long COVID\'s cognitive, neurological, and psychiatric symptoms and their potential impact on brain stimulation and neuroimaging studies. It argues that researchers must adapt their study designs and screening processes to account for the confounding effects of long COVID and ensure the accuracy and reliability of their findings. To advance the understanding of this condition and its long-term effects on brain health, the review proposes a series of strategies, including the development of standardized screening tools, the investigation of underlying mechanisms, and the identification of risk factors and protective factors. It also emphasizes the importance of collaborative research efforts and international data sharing platforms in accelerating the pace of discovery and developing targeted interventions for individuals with long COVID. As the prevalence of this condition continues to grow, it is imperative that the neuroscience community comes together to address this challenge and support those affected by long COVID.
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  • 文章类型: Journal Article
    注意力功能下降会导致日常生活中的问题。然而,一种快速简便的注意力功能评估方法尚未开发出来。因此,我们正在寻找一种简单、快速地评估注意功能的方法。本研究旨在收集有关注意任务期间脑电图(EEG)特征的基本数据,以开发一种使用EEG评估注意功能的新方法。20名健康的年轻人参加了;我们在使用便携式EEG设备进行临床注意力评估期间检查了大脑活动。进行Mann-WhitneyU检验以评估低注意力组和高注意力组之间在任务期间EEG功率水平的差异。研究结果表明,高度关注组显示在L-颞叶和双侧顶叶的δ波中的EEG功率水平明显更高,以及在R枕叶的β和γ波中,比数字向前的低注意力组要多,而高度关注组的R-额叶的θ波和双侧额叶的α波在向后指期间显示出显着更高的EEG功率水平。值得注意的是,下θ,α,在低注意力组中发现的右半球β带可能是检测注意力缺陷的关键因素。
    Decreased attentional function causes problems in daily life. However, a quick and easy evaluation method of attentional function has not yet been developed. Therefore, we are searching for a method to evaluate attentional function easily and quickly. This study aimed to collect basic data on the features of electroencephalography (EEG) during attention tasks to develop a new method for evaluating attentional function using EEG. Twenty healthy young adults participated; we examined cerebral activity during a Clinical Assessment for Attention using portable EEG devices. The Mann-Whitney U test was performed to assess differences in power levels of EEG during tasks between the low- and high-attention groups. The findings revealed that the high-attention group showed significantly higher EEG power levels in the δ wave of L-temporal and bilateral parietal lobes, as well as in the β and γ waves of the R-occipital lobe, than did the low-attention group during digit-forward, whereas the high-attention group showed significantly higher EEG power levels in the θ wave of R-frontal and the α wave of bilateral frontal lobes during digit-backward. Notably, lower θ, α, and β bands of the right hemisphere found in the low-attention group may be key elements to detect attentional deficit.
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  • 文章类型: Journal Article
    经颅直流电刺激(tDCS)的神经生物学作用尚未明确阐明。一些研究表明,在额下回(IFG)上使用tDCS可以增强健康和神经系统个体的认知功能。在目标区域及其神经周围施加神经变化。在这次系统审查中,我们通过数据库搜索选择了健康和神经系成年人的随机假对照试验,以探索IFG上的tDCS结合认知训练是否调节功能连接或神经变化.最终纳入了20项研究,其中12项通过功能磁共振(fMRI)测量了TDCS效应,二通过功能近红外光谱(fNIRS),和六个通过脑电图(EEG)。由于在研究中观察到的高度异质性,对数据进行定性描述和比较以评估可靠性.总的来说,结合fMRI和tDCS的研究显示,局部和远处大脑区域的功能连接发生了广泛的变化。研究结果还表明,tDCS还可以调节目标区域下方的电生理变化。然而,这些结局并不总是伴随着相应的显著行为结果.这项工作提出了关于tDCS的一般功效的问题,其含义延伸到稳步增加的tDCS文献。
    The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature.
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  • 文章类型: Journal Article
    背景:脑脊液(CSF)中在骨髓细胞2(sTREM2)上表达的可溶性触发受体被认为是小胶质细胞活性的生物标志物。这项研究的目的是调查CSFsTREM2水平随时间的变化轨迹,并检查其与性别的关系。
    方法:纳入了1,017名来自阿尔茨海默病神经影像学倡议研究(ADNI)的参与者,其中至少有一个CSFsTREM2记录。使用生长曲线模型分析CSFsTREM2的轨迹。使用线性混合效应模型评估CSFsTREM2水平与性别之间的关联。
    结果:CSFsTREM2水平随年龄增长而升高(P<0.0001)。在整个样本中,sTREM2水平没有观察到显著的性别差异;然而,在APOEε4等位基因携带者中,女性sTREM2水平显著高于男性(β=0.146,P=0.002).
    结论:我们的发现强调了CSFsTREM2水平与年龄相关的增量之间的关联,强调衰老对sTREM2动力学的潜在影响。此外,我们的观察表明性别和CSFsTREM2水平之间存在显著关联,特别是在携带APOEε4等位基因的个体中。
    BACKGROUND: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is considered a biomarker of microglia activity. The objective of this study was to investigate the trajectory of CSF sTREM2 levels over time and examine its association with sex.
    METHODS: A total of 1,017 participants from the Alzheimer\'s Disease Neuroimaging Initiative Study (ADNI) with at least one CSF sTREM2 record were included. The trajectory of CSF sTREM2 was analyzed using a growth curve model. The association between CSF sTREM2 levels and sex was assessed using linear mixed-effect models.
    RESULTS: CSF sTREM2 levels were increased with age over time (P < 0.0001). No significant sex difference was observed in sTREM2 levels across the entire sample; however, among the APOE ε4 allele carriers, women exhibited significantly higher sTREM2 levels than men (β = 0.146, P = 0.002).
    CONCLUSIONS: Our findings highlight the association between CSF sTREM2 levels and age-related increments, underscoring the potential influence of aging on sTREM2 dynamics. Furthermore, our observations indicate a noteworthy association between sex and CSF sTREM2 levels, particularly in individuals carrying the APOE ε4 allele.
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  • 文章类型: Journal Article
    背景:为了评估Omicron感染引起的神经系统改变,比较Omicron患者慢性失眠与慢性失眠加剧的大脑变化,并检查没有失眠的人以及新发失眠的人。
    方法:在本研究中,在2023年1月11日至5月4日期间共招募了135名参与者,其中包括26名没有恶化的慢性失眠患者,24例慢性失眠患者加重,40例无睡眠障碍患者,以及30例感染Omicron后出现新发失眠的患者(共120例患者感染后睡眠状态不同),以及15名从未感染过Omicron的健康对照。神经精神病学数据,临床症状,并收集了多模态磁共振成像数据。灰质厚度与T1、T2、质子密度、和血管周围空间值进行分析。通过相关性分析评估了多模态磁共振成像结果的变化与神经精神病学数据之间的关联。
    结果:与健康对照组相比,感染后有和没有慢性失眠史的患者的灰质厚度变化相似,包括顶叶附近皮质厚度的增加和额叶皮质厚度的减少,枕骨,和内侧大脑区域。分析表明,与Omicron感染后慢性失眠加重的患者相比,慢性失眠患者的灰质厚度降低,并且在右侧内侧眶额叶区域发现了减少(平均值[SD],2.38[0.17]vs.2.67[0.29]mm;P<0.001)。在Omicron患者睡眠恶化的亚组中,有慢性失眠病史的患者,在感染后失眠症状恶化,表现为内侧眶额皮质厚度增加,不同脑区的质子密度值增加。相反,睡眠质量良好的患者在感染后出现了新的失眠,其表现为钙皮区域的皮质厚度减少,质子密度值降低。在Omicron感染后的新发失眠患者中,右侧果皮厚度与焦虑自评量表(r=-0.538,P=0.002,PFDR=0.004)和抑郁自评量表(r=-0.406,P=0.026,PFDR=0.026)评分呈负相关。
    结论:这些发现有助于我们理解Omicron侵入神经系统并在感染后诱发各种形式的失眠所涉及的病理生理机制。在未来,我们将继续关注与Omicron感染引起的失眠相关的大脑动态变化。
    BACKGROUND: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia.
    METHODS: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses.
    RESULTS: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r =  - 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r =  - 0.406, P = 0.026, PFDR = 0.026) scores.
    CONCLUSIONS: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.
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  • 文章类型: Journal Article
    背景:常染色体隐性遗传原发性小头畸形(MCPH)是一种罕见的神经发育和遗传异质性疾病,以颅骨小(>-3SD低于平均值)为特征,通常会导致不同程度的智力残疾。由于其临床和遗传异质性,已鉴定出30种基因用于该疾病的病因。
    结果:这里,我们报告了两个受MCPH影响的巴基斯坦近亲家庭,其在WDR62基因中表现出突变。研究方法涉及下一代测序(NGS)基因组测序与连锁分析结合,随后通过自动Sanger测序和条形码标记(BT)测序验证鉴定的变体。分子遗传分析揭示了家族A中的一个新的剪接位点变体(NM_001083961.2(WDR62):c.1372-1del)和一个已知的外显子变体NM_001083961.2(WDR62):c.3936dup(p家庭B中的Val1313Argfs*18)。磁共振成像(MRI)扫描也被用来了解受影响个体的结构架构。神经系统评估显示,受影响的个体具有新的变异体,其回旋和沟模式减少以及正常的call体。使用不同的工具对鉴定的变体进行计算机评估以确认这些变体的致病性。通过硅分析,这两种变体均被鉴定为致病的,外显子变体的蛋白质模型显示预言的蛋白质结构有细微的构象改变.
    结论:这项研究确定了一种新的变异体(c.1372-1del)和一种复发性致病性变异体c.3936dup(p。Val1313Argfs*18)在巴基斯坦人群中的WDR62基因中,扩大MCPH的突变谱。这些发现强调了遗传咨询和意识对减少血缘关系和解决这种疾病负担的重要性。
    BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental and genetically heterogeneous disorder, characterized by small cranium size (> - 3 SD below mean) and often results in varying degree of intellectual disability. Thirty genes have been identified for the etiology of this disorder due to its clinical and genetic heterogeneity.
    RESULTS: Here, we report two consanguineous Pakistani families affected with MCPH exhibiting mutation in WDR62 gene. The investigation approach involved Next Generation Sequencing (NGS) gene panel sequencing coupled with linkage analysis followed by validation of identified variants through automated Sanger sequencing and Barcode-Tagged (BT) sequencing. The molecular genetic analysis revealed one novel splice site variant (NM_001083961.2(WDR62):c.1372-1del) in Family A and one known exonic variant NM_001083961.2(WDR62):c.3936dup (p.Val1313Argfs*18) in Family B. Magnetic Resonance Imaging (MRI) scans were also employed to gain insights into the structural architecture of affected individuals. Neurological assessments showed the reduced gyral and sulcal patterns along with normal corpus callosum in affected individuals harboring novel variant. In silico assessments of the identified variants were conducted using different tools to confirm the pathogenicity of these variants. Through In silico analyses, both variants were identified as disease causing and protein modeling of exonic variant indicates subtle conformational alterations in prophesied protein structure.
    CONCLUSIONS: This study identifies a novel variant (c.1372-1del) and a recurrent pathogenic variant c.3936dup (p.Val1313Argfs*18) in the WDR62 gene among the Pakistani population, expanding the mutation spectrum for MCPH. These findings emphasize the importance of genetic counseling and awareness to reduce consanguinity and address the burden of this disorder.
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