Clinica Chimica Acta最新文献_第6页

Corrigendum to "Sex based profiles in serum and urine levels of major VEGF-A isoforms, VEGF-A₁₂₁ and VEGF-A₁₆₅" [Clin. Chim. Acta. 578 (2026) 120576]. “主要VEGF-A亚型，VEGF-A121和VEGF-A165的血清和尿液中基于性别的特征”[临床]的更正。詹。学报，578(2026):120576]。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-15 Epub Date: 2025-10-16 DOI: 10.1016/j.cca.2025.120652

Ryosuke Kikuchi, Shingo Yamada, Hidekazu Ishida, Masahiro Nakatochi, Yumiko Kobayashi, Yuki Ohashi, Kazuhiko Kotani, Atsuo Suzuki, Yohei Shirakami, Takatomo Watanabe, Hiroyuki Okura

引用次数: 0

Corrigendum to "Do PHI and PHI density improve detection of clinically significant prostate cancer only in the PSA gray zone?" [Clin. Chim. Acta 542 (2023) 117270]. “PHI和PHI密度是否仅在PSA灰色地带提高临床显著前列腺癌的检出率？”的勘误表。(中国。詹。学报542(2023)117270]。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-15 Epub Date: 2025-09-16 DOI: 10.1016/j.cca.2025.120590

Leire Rius Bilbao, Carmen Valladares Gomez, Urko Aguirre Larracoechea, Jose Gregorio Pereira Arias, Pablo Arredondo Calvo, Luis Felipe Urdaneta Salegui, Victor Escobal Tamayo, Juan Pablo Sanz Jaka, Adrian Recio Ayesa, Javier Mar Medina, Carmen Mar Medina

引用次数: 0

Corrigendum to "HbA1c: Gender & age differences in non-diabetic Saudi children & adults in Alqassim Buraidah region" [Clin. Chim. Acta 558(Supplement 1) (2024) 118001]. “HbA1c: Alqassim Buraidah地区非糖尿病沙特儿童和成人的性别和年龄差异”的勘误表。詹。学报（补编1）（2024）118001]。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-15 Epub Date: 2025-10-14 DOI: 10.1016/j.cca.2025.120648

A Alrashedi, Ghada M K Gaballah

引用次数: 0

NMR-based metabolomics reveals distinct metabolic profiles in juvenile systemic lupus erythematosus and juvenile idiopathic arthritis 基于核磁共振的代谢组学揭示了青少年系统性红斑狼疮和青少年特发性关节炎的不同代谢特征

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-14 DOI: 10.1016/j.cca.2026.120836

Jeferson S. Ursulino , Edmilson R.R. Junior , Larissa S. Pinto , Paula Sandrin-Garcia , Denise Q. Nascimento , Thiago S. Fragoso , Thiago M. Aquino

Background

Juvenile systemic lupus erythematosus (jSLE) and juvenile idiopathic arthritis (jIA) are chronic autoimmune diseases with overlapping clinical manifestations, making early and accurate diagnosis challenging. This study aimed to utilize proton nuclear magnetic resonance (¹H NMR)-based metabolomics to identify potential plasma biomarkers that can differentiate between jSLE, jIA, and healthy pediatric individuals.

Materials and methods

A total of 75 plasma samples were analyzed, including 28 from jSLE patients, 10 from jIA patients, and 37 from healthy controls. Metabolic profiling was performed using ¹H NMR spectroscopy. Multivariate statistical analyses, including PCA, sPLS-DA, and OPLS-DA, were applied to identify disease-specific metabolic patterns. Diagnostic performance was evaluated using univariate and multivariate ROC curve analysis, with model validation through cross-validation and permutation testing.

Results

Distinct metabolic profiles were observed among the three groups. In the pairwise comparisons, a proposed diagnostic panel of key metabolites, including tyrosine, formate, histidine, isoleucine, and glucose, demonstrated excellent discriminative power. Univariate ROC analysis identified several metabolites with perfect discriminative capacity (AUC = 1.0) between jSLE or jIA and controls, such as tyrosine, formate, histidine, acetone, and lactate. In the comparison between jSLE and jIA, nine metabolites showed AUC > 0.91. Multivariate ROC curve analysis using PLS-DA and SVM classifiers with 5-fold cross-validation achieved outstanding classification performance, with AUC values reaching 1.0 for control vs. jSLE and control vs. jIA (using 5, 7, 10, and 16 metabolites), and 0.99 for jSLE vs. jIA. For all models, significant model fit and predictive capability (R² and Q(Groot et al., 2017²)) were found (p < 0.001), indicating robust model stability and strong predictive power. Collectively, the panel of five biomarkers yielded an AUC > 0.95 in all comparisons, highlighting its strong diagnostic potential.

Conclusion

This study identified metabolic biomarkers with strong diagnostic potential for differentiating jSLE, jIA, and healthy controls using NMR-based metabolomics. These findings offer promising tools for early differential diagnosis and lay the groundwork for future translational research in pediatric autoimmune diseases.

背景：幼年系统性红斑狼疮（jSLE）和幼年特发性关节炎（jIA）是两种具有重叠临床表现的慢性自身免疫性疾病，早期准确诊断具有一定的挑战性。本研究旨在利用基于质子核磁共振（1H NMR）的代谢组学来鉴定潜在的血浆生物标志物，以区分jSLE、jIA和健康儿童个体。材料与方法共分析75份血浆样本，其中jSLE患者28份，jIA患者10份，健康对照37份。利用1H NMR谱进行代谢谱分析。多变量统计分析，包括PCA、sPLS-DA和OPLS-DA，用于识别疾病特异性代谢模式。采用单变量和多变量ROC曲线分析评估诊断效果，并通过交叉验证和排列检验对模型进行验证。结果三组小鼠代谢谱差异明显。在两两比较中，提出的关键代谢物诊断小组，包括酪氨酸、甲酸盐、组氨酸、异亮氨酸和葡萄糖，显示出出色的鉴别能力。单因素ROC分析发现，jSLE或jIA与对照组的代谢物具有完全判别能力（AUC = 1.0），如酪氨酸、甲酸盐、组氨酸、丙酮和乳酸盐。jSLE与jIA比较，9个代谢物AUC >； 0.91。采用5倍交叉验证的PLS-DA和SVM分类器进行多变量ROC曲线分析，分类效果显著，对照与jSLE和对照与jIA（分别使用5、7、10和16种代谢物）的AUC值达到1.0，jSLE与jIA的AUC值达到0.99。所有模型均具有显著的模型拟合和预测能力（R2和Q(Groot et al., 20172)）（p < 0.001），表明模型稳定性强，预测能力强。总的来说，五种生物标志物在所有比较中产生了0.95的AUC，突出了其强大的诊断潜力。结论：本研究利用基于核磁共振的代谢组学鉴定出具有很强诊断潜力的代谢生物标志物，可用于鉴别jSLE、jIA和健康对照。这些发现为早期鉴别诊断提供了有希望的工具，并为未来儿童自身免疫性疾病的转化研究奠定了基础。

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引用次数: 0

Tissue polypeptide antigen as a non-invasive bladder Cancer biomarker 组织多肽抗原作为非侵入性膀胱癌的生物标志物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-13 DOI: 10.1016/j.cca.2026.120843

Neeraj Kumar Fuloria , Kamal Narain , Anupam Biswas , Padmashini Gnanam , Satish Vasanth Dhandapani , Sangita Biswas , Sumita Bhatia , Shivkanya Fuloria

Tissue Polypeptide Antigen (TPA), a non-invasive biomarker comprising fragments of cytokeratins 8, 18, and 19, has demonstrated potential for non-invasive surveillance of bladder cancer. However, challenges related to standardization impede its clinical implementation. This narrative review provides a focused overview of the relationship between TPA molecular biology and clinical laboratory practice, with special emphasis on analytical standardization, preanalytical harmonization, and evidence-based diagnostic algorithms. Urinary TPA has a sensitivity of 80–85% and specificity of 97% in optimized protocols of high-risk non-muscle-invasive bladder cancer (NMIBC), generally outperforming serum TPA in detecting invasive disease and monoclonal chemiluminescent assays have intra-assay variation of less than 5% and inter-method bias of 20–30%. The use of TPA, in conjunction with cytology and immunocytochemistry for multiple markers, demonstrated a diagnostic area under the curve exceeding 0.90. Furthermore, compartment-specific TPA in serum and urine compartments substantiates its role as an indicator of overall tumor burden and local disease activity in muscle-invasive bladder cancer (MIBC). Priorities in clinical implementation involve the use of IFCC-aligned standardized preanalytical operations in accordance with IFCC guidelines, laboratory-specific cutoff testing, external quality assurance harmonization with commutable reference materials, and assay-specific clinical decision limits. TPA is a useful biomarker for compartment-specific surveillance and is best utilized within multi-marker algorithms in routine laboratory procedures rather than as a stand-alone marker. To optimize its application in clinical laboratories, further research is needed on its cost-effectiveness and the potential reduction of TPA-directed cystoscopy in risk-stratified cohorts.

组织多肽抗原（TPA）是一种由细胞角蛋白8、18和19片段组成的非侵入性生物标志物，已被证明具有膀胱癌非侵入性监测的潜力。然而，与标准化相关的挑战阻碍了其临床应用。这篇叙述性综述提供了TPA分子生物学与临床实验室实践之间关系的重点概述，特别强调分析标准化、分析前协调和循证诊断算法。尿TPA在高危非肌浸润性膀胱癌（NMIBC）优化方案中的敏感性为80-85%，特异性为97%，在检测浸润性疾病方面普遍优于血清TPA，单克隆化学发光法检测内变异小于5%，方法间偏差为20-30%。使用TPA，结合细胞学和免疫细胞化学的多种标记物，显示曲线下的诊断区域超过0.90。此外，血清和尿液间室特异性TPA证实了其作为肌肉浸润性膀胱癌（MIBC）总体肿瘤负荷和局部疾病活动性指标的作用。临床实施的优先事项包括根据IFCC指南使用与IFCC一致的标准化分析前操作、实验室特定的截止检测、外部质量保证与可交换参考物质的协调以及检测特定的临床决策限制。TPA是一种有用的生物标志物，用于室特异性监测，最好在常规实验室程序中的多标记算法中使用，而不是作为单独的标记。为了优化其在临床实验室中的应用，需要进一步研究其成本效益以及在风险分层队列中减少tpa定向膀胱镜检查的可能性。

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引用次数: 0

The commutability of thyroid-stimulating hormone international reference preparations plays an important role in metrological traceability 促甲状腺激素国际标准制剂的可交换性在计量溯源中起着重要作用

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-13 DOI: 10.1016/j.cca.2026.120842

Shunli Zhang , Fei Cheng , Hua Wang , Mo Wang , Rui Zhang , Yuhong Yue , Qingtao Wang

Objectives

This study aimed to assess the commutability of thyroid-stimulating hormone (TSH) international reference preparations (IRP) among various assays and to elucidate their role in achieving metrological traceability across systems.

Methods

We evaluated the commutability of TSH 3rd IRP 81/565, dissolved in eleven different diluents to achieve two to three different TSH concentrations. The assessment involved 29 serum samples across eight clinical laboratory measurement procedures (CLMP) following the CLSI EP30-A guidelines. Furthermore, 11 different TSH concentrations candidate standard materials prepared from human serum pools (HSPs) were prepared and assigned values from a series of reconstituted IRPs to clarify practical significance of commutable reconstituted IRPs. Two more CLMPs were used to assign values for 11 candidate standard materials using TSH IRP to verify applicability of the diluents.

Results

The TSH IRP demonstrated variable commutability in the eleven diluents, with no single diluent achieving commutability across all assay platforms. Notably, we recorded significant biases of approximately 25.5% and −23.2% when utilizing uncommutable matrices(the TSH IRP were not commutable between CLMPs in these matrices) for value assignments of HSPs via CI 1000 and Cobas 601 assays, respectively. Lastly, Harmonized TSH assigned values ranged from 0.191 μIU/mL to 44.985 μIU/mL, with uncertainties varying between 0.039 μIU/mL and 3.523 μIU/mL using 10 CLMP including 13 methods for 11 different TSH concentration candidate standard materials.

Conclusions

The commutability of TSH IRP is crucial for assigning TSH values in clinical practice. The matrices employed for dissolving IRPs present significant challenges in securing commutability, but their influence is vital for TSH multisystem metrological traceability.

目的本研究旨在评估促甲状腺激素（TSH）国际标准制剂（IRP）在各种检测方法中的可交换性，并阐明其在实现跨系统计量可追溯性中的作用。方法我们评估了TSH 3irp 81/565的交换性，将其溶解在11种不同的稀释剂中，以获得2到3种不同的TSH浓度。根据CLSI EP30-A指南，评估涉及8个临床实验室测量程序（CLMP）的29个血清样本。此外，从人血清池（HSPs）中制备了11种不同TSH浓度的候选标准材料，并从一系列重组IRPs中赋值，以阐明可交换重组IRPs的实际意义。另外两个clmp使用TSH IRP对11个候选标准材料赋值，以验证稀释剂的适用性。结果TSH IRP在11种稀释剂中表现出可变的交换性，没有一种稀释剂在所有检测平台上实现交换性。值得注意的是，当使用不可交换矩阵（TSH IRP在这些矩阵中的clmp之间不可交换）时，我们分别通过CI 1000和Cobas 601检测记录了大约25.5%和- 23.2%的显著偏差。最后，采用10种CLMP方法对11种不同TSH浓度的候选标准物质进行测定，统一TSH分配值在0.191 ~ 44.985 μIU/mL之间，不确定度在0.039 ~ 3.523 μIU/mL之间。结论TSH IRP的可交换性是临床上确定TSH值的关键。用于溶解irp的矩阵在确保可交换性方面提出了重大挑战，但它们对TSH多系统计量可追溯性的影响至关重要。

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引用次数: 0

GDF-15 as an integrative cardiometabolic biomarker GDF-15作为一种综合性心脏代谢生物标志物。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-13 DOI: 10.1016/j.cca.2026.120839

Obaid Afzal , Muhammad Afzal , Nawaid Hussain Khan , Ali Altharawi , Mubarak A. Alamri , Manal A. Alossaimi , Abdulmalik S.A. Altamimi , Pavan Goud

Growth Differentiation Factor 15 (GDF-15) is a stress-inducible cytokine that is abundantly expressed in cardiomyocytes, adipose tissue, macrophages, endothelial cells, and vascular smooth muscle cells. The levels of this biomarker increase in response to tissue injury, inflammation, and metabolic stress and are elevated in the presence of primary cardiometabolic diseases, such as type 2 diabetes, obesity, hypertension, atherosclerosis, heart failure, and chronic kidney disease. This is articulated in a clinical chemistry narrative review, which elucidates why GDF-15 can be characterized as an integrative biomarker. This characterization is due to the shared pathophysiological processes of metabolic stress, inflammation, oxidative/mitochondrial stress, and tissue injury across these conditions, as well as its clinical applications in risk assessment, prognosis, and monitoring. We also briefly present modern methods to measure circulating GDF-15 (primarily immunoassays, with new mass-spectrometry techniques being developed) and note that inter-assay variability and assay standardization are considered to be the major impediments to clinical application. The most significant determinants of biological variability (age, sex, renal function, genetic variation, and comorbidities), by which reference intervals and longitudinal interpretation are affected, are also highlighted. Increased GDF-15 is consistently associated with poor outcomes in diabetes, obesity, hypertension, heart failure, and atherosclerosis, such as cardiovascular events, kidney failure, and death. Nonetheless, prognostic cutoffs have been proposed variably across studies, populations, and measurement platforms. Therefore, these thresholds should be approached with caution until harmonized assays and clinically validated decision limits established through prospective studies are available. GDF-15 is a powerful integrative biomarker of metabolic stress, inflammation, and tissue injury in cardiometabolic diseases. Its introduction into clinical practice may enhance early risk stratification, personalize therapeutic interventions and monitor disease progression. Future studies should focus on optimizing the standardization of assays, developing evidence-based reference intervals (and reference change values), and elucidating clinically practical decision limits and therapeutic implications of the GDF-15 pathway in the treatment of cardiometabolic diseases.

生长分化因子15 （Growth Differentiation Factor 15, GDF-15）是一种应激诱导型细胞因子，在心肌细胞、脂肪组织、巨噬细胞、内皮细胞和血管平滑肌细胞中大量表达。该生物标志物的水平在组织损伤、炎症和代谢应激反应中升高，在原发性心脏代谢疾病（如2型糖尿病、肥胖、高血压、动脉粥样硬化、心力衰竭和慢性肾病）存在时升高。这在一篇临床化学叙述性综述中得到了阐述，该综述阐明了为什么GDF-15可以被描述为一种综合生物标志物。这一特征是由于代谢应激、炎症、氧化/线粒体应激和组织损伤在这些条件下的共同病理生理过程，以及其在风险评估、预后和监测方面的临床应用。我们还简要介绍了测量循环GDF-15的现代方法（主要是免疫测定，以及正在开发的新的质谱技术），并注意到测定间的可变性和测定标准化被认为是临床应用的主要障碍。生物变异的最重要决定因素（年龄、性别、肾功能、遗传变异和合并症）也受到了参考区间和纵向解释的影响。GDF-15升高一直与糖尿病、肥胖、高血压、心力衰竭和动脉粥样硬化（如心血管事件、肾衰竭和死亡）的不良结局相关。尽管如此，在不同的研究、人群和测量平台上提出的预后截止点是不同的。因此，在通过前瞻性研究建立统一的分析和临床验证的决策限制之前，应该谨慎处理这些阈值。GDF-15是心血管代谢疾病中代谢应激、炎症和组织损伤的强大综合生物标志物。将其引入临床实践可以加强早期风险分层，个性化治疗干预和监测疾病进展。未来的研究应侧重于优化检测方法的标准化，建立基于证据的参考区间（和参考变化值），并阐明GDF-15途径在治疗心脏代谢疾病中的临床实践决策限制和治疗意义。

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引用次数: 0

Klotho protein and insulin resistance Klotho蛋白和胰岛素抵抗

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-12 DOI: 10.1016/j.cca.2026.120840

Yaqin Cai , Bin Liu , Dandan Song , Yulong Zhao , Bibo Xie , Yingping Zhang , Yuqiu Zhou

Klotho was initially identified as an anti-ageing protein expressed mainly in renal distal tubular cells and the choroid plexus. The Klotho family comprises several members, including α-Klotho (αKl), β-Klotho (βKl), Klotho-LPH related protein (KLPH; lactase-phlorizin hydrolase), and Klotho-related protein (KlrP), which perform a multitude of functions related to various physiological processes. The effects of Klotho on various ageing-related and renal diseases, such as its antiapoptotic effects, ability to reduce oxidative stress, anti-inflammatory effects, and other functions, have extensively been reviewed, suggesting the significant cardiorenal benefits of Klotho. Klotho expression deficiency promotes age-related pathology and is correlated with renal impairment. Studies have shown that serum Klotho is significantly decreased in type 2 diabetes (T2DM) and is linked to the duration of diabetes, indicating that Klotho may be involved in multiple pathological mechanisms of T2DM. Insulin resistance (IR) plays an essential role in the onset and progression of T2DM. Research has demonstrated that the expression of Kl is closely correlated with insulin secretion, insulin signaling pathways, and insulin sensitivity and may serve as a potential predictive marker for the IR and diabetes risk. We comprehensively reviewed the relevant literature in PubMed using the keywords “Klotho”, “Type 2 diabetes”, and “Insulin resistance”. This review summarizes the relationship between Klotho and IR.

Klotho最初被认为是一种主要表达于肾远端小管细胞和脉络膜丛的抗衰老蛋白。Klotho家族包括α-Klotho （αKl）、β-Klotho （βKl）、Klotho- lph相关蛋白（KLPH; lactase-phlorizin hydrolase）和Klotho相关蛋白（KlrP）等几个成员，它们在各种生理过程中发挥着多种功能。Klotho对各种衰老相关疾病和肾脏疾病的影响，如其抗凋亡作用、减少氧化应激的能力、抗炎作用和其他功能，已经被广泛地回顾，表明Klotho对心脏肾脏有显著的益处。Klotho表达缺乏促进与年龄相关的病理，并与肾脏损害相关。研究表明，2型糖尿病（T2DM）患者血清Klotho显著降低，且与糖尿病病程有关，提示Klotho可能参与T2DM的多种病理机制。胰岛素抵抗（IR）在T2DM的发生和发展中起着重要作用。研究表明，Kl的表达与胰岛素分泌、胰岛素信号通路和胰岛素敏感性密切相关，可能是IR和糖尿病风险的潜在预测指标。我们以关键词“Klotho”、“Type 2 diabetes”、“Insulin resistance”综合检索PubMed相关文献。本文就Klotho与IR的关系作一综述。

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引用次数: 0

Clinical utilization of beta-hydroxybutyrate and comparison with urine ketones in a quaternary care health system -羟基丁酸酯与尿酮在四级保健系统中的临床应用及比较

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-12 DOI: 10.1016/j.cca.2026.120838

Maxwell L. Harsha , Mary Ann Ness , Mark A. Marzinke

Blood beta-hydroxybutyrate (BHB) and urine ketones (UK) are key biomarkers for assessing ketosis, including life-threatening diabetic ketoacidosis (DKA). BHB is the primary ketone produced during ketotic states and shows greater sensitivity and specificity than UK, which do not detect BHB. Current professional guidelines recommend BHB testing over UK for assessing DKA. This study retrospectively examined the utilization of serum BHB and its clinical performance compared to UK over a one-year period within our quaternary care healthcare system.

BHB ordering metrics and patient demographics were obtained from the electronic health record system between November 1, 2023, and October 31, 2024. The clinical performance of BHB compared to UK was assessed through concordance analysis of specimens collected within one hour of each other, alongside comparisons to other serum analytes and chart review of patients with discordant BHB and UK results.

During the one-year period, our academic medical center's laboratory performed 3235 BHB tests from 2011 unique patients. The majority of tests were performed on adults over 60 years of age (42%) in high-acuity settings (64%), and for patients exhibiting DKA symptoms (86%). Concordance analysis revealed that 24% of BHB and UK contemporaneously ordered results were discordant, with the majority showing elevated BHB concentrations and normal UK results. Assessment of this discordant group suggested that kidney function may may be a driving factor of observed discrepancies.

These findings align with existing guidelines and highlight the need for further investigation of BHB utilization in specific populations, such as surgical and medically complex patients.

血液β -羟基丁酸酯（BHB）和尿酮（UK）是评估酮症的关键生物标志物，包括危及生命的糖尿病酮症酸中毒（DKA）。BHB是在酮症状态下产生的主要酮，比UK具有更高的敏感性和特异性，而UK没有检测到BHB。目前的专业指南建议在英国进行BHB测试来评估DKA。本研究回顾性检查了血清BHB的利用率及其临床表现，与英国在我国四级医疗保健系统的一年期间进行了比较。从2023年11月1日至2024年10月31日期间的电子健康记录系统中获得BHB订购指标和患者人口统计数据。BHB与UK的临床表现是通过一小时内采集标本的一致性分析，以及与其他血清分析物的比较和BHB与UK结果不一致的患者的图表回顾来评估的。在一年的时间里，我们学术医学中心的实验室对2011例独特患者进行了3235次BHB检测。大多数测试是在60岁以上的成年人（42%）和有DKA症状的患者（86%）中进行的。一致性分析显示24%的BHB和UK同时排序结果不一致，大多数显示BHB浓度升高而UK结果正常。对这一不一致组的评估表明，肾功能可能是观察到的差异的驱动因素。这些发现与现有指南一致，并强调需要进一步调查BHB在特定人群中的使用情况，例如手术和医学复杂的患者。

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引用次数: 0

Frameshift variants in the UBTF gene are associated with neurodevelopmental disorders UBTF基因中的移码变异与神经发育障碍有关

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2026-01-12 DOI: 10.1016/j.cca.2026.120841

Sheng Yi , Lingyun Fan , Qiang Zhang , Xiuliang Rong , Junjie Chen , Qi Yang , Shujie Zhang , Xunzhao Zhou , Shang Yi , Jingsi Luo , Qinle Zhang , Zailong Qin

Background

The Upstream Binding Transcription Factor (UBTF) gene encodes a nucleolar phosphoprotein characterized by the presence of both DNA-binding and transactivation domains. Mutations in the UBTF gene have been implicated in a variety of pathological conditions. Specifically, recurrent de novo heterozygous missense mutations in UBTF have been linked to childhood onset neurodegeneration with brain atrophy, whereas UBTF haploinsufficiency has been associated with global developmental delay and distinctive facial features in the absence of neuroregression.

Methods

This study involved the recruitment of two unrelated individuals exhibiting psychomotor developmental delay and intellectual disability. Exome sequencing was performed to identify potential genetic variants. Additionally, RNA analysis was employed to assess the effects of these genetic variants on gene expression.

Results

Both subjects demonstrated language impairments and intellectual disability without evidence of neuroregression. One individual experienced epilepsy and unilateral cerebellar dysplasia, while the other exhibited microcephaly, hypertonia, and psychosis. Genetic analysis identified two distinct frameshift variants in the UBTF gene, specifically c.2104del (p.Ser702Profs*83) and c.1199del (p.Gly400Alafs*38). RNA analysis of a peripheral blood sample demonstrated a decreased expression level of the mutant transcript. Furthermore, multiple alternative splicing events within the UBTF gene were observed in peripheral blood. Additionally, a systematic evaluation based on ClinGen criteria established a “Strong” gene-disease association between loss-of-function variants in UBTF and a neurodevelopmental delay without neuroregression.

Conclusions

The findings of this study expand the known genetic and phenotypic spectrum of neurological disorders associated with UBTF haploinsufficiency. These results contribute valuable insights toward elucidating the genotype-phenotype correlations underlying this condition.

上游结合转录因子（UBTF）基因编码一种核仁磷酸化蛋白，其特征是存在dna结合和反活化结构域。UBTF基因的突变与多种病理状况有关。具体来说，复发性从头杂合错义突变与儿童期神经退行性变伴脑萎缩有关，而在没有神经退行性变的情况下，UBTF单倍功能不全与整体发育迟缓和独特的面部特征有关。方法本研究招募了两名精神运动发育迟缓和智力残疾的非亲属个体。外显子组测序鉴定潜在的遗传变异。此外，采用RNA分析来评估这些遗传变异对基因表达的影响。结果两组患者均有语言障碍和智力障碍，无神经功能退化。一个人经历癫痫和单侧小脑发育不良，而另一个表现为小头畸形、高张力和精神病。遗传分析在UBTF基因中发现了两个不同的移码变体，特别是c.2104del （p.Ser702Profs*83）和c.1199del （p.Gly400Alafs*38）。外周血样本的RNA分析显示突变转录物的表达水平降低。此外，在外周血中观察到UBTF基因内的多个选择性剪接事件。此外，基于ClinGen标准的系统评估在UBTF的功能丧失变体和无神经退化的神经发育延迟之间建立了“强”基因-疾病关联。结论本研究的发现扩大了与UBTF单倍功能不全相关的神经系统疾病的已知遗传和表型谱。这些结果为阐明这种情况下的基因型-表型相关性提供了宝贵的见解。

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引用次数: 0