Castells Alba-Aina, Balada Rafel, Tristán-Noguero Alba, O'Callaghan Mar, Cortès-Saladelafont Elisenda, Pascual-Alonso Ainhoa, Garcia-Cazorla Àngels, Armstrong Judith, Alcántara Soledad
Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, l'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain.
Biomedicines. 2021 Feb 3;9(2):148. doi: 10.3390/biomedicines9020148.
Methyl-CpG-binding protein 2 (MeCP2) is an X-linked epigenetic modulator whose dosage is critical for neural development and function. Loss-of-function mutations in cause Rett Syndrome (RTT, OMIM #312750) while duplications in the Xq28 locus containing and Interleukin-1 receptor-associated kinase 1 () cause duplication syndrome (MDS, OMIM #300260). Both are rare neurodevelopmental disorders that share clinical symptoms, including intellectual disability, loss of speech, hand stereotypies, vasomotor deficits and seizures. The main objective of this exploratory study is to identify novel signaling pathways and potential quantitative biomarkers that could aid early diagnosis and/or the monitoring of disease progression in clinical trials. We analyzed by RT-PCR gene expression in whole blood and microRNA (miRNA) expression in plasma, in a cohort of 20 females with Rett syndrome, 2 males with duplication syndrome and 28 healthy controls, and correlated RNA expression with disease and clinical parameters. We have identified a set of potential biomarker panels for RTT diagnostic and disease stratification of patients with microcephaly and vasomotor deficits. Our study sets the basis for larger studies leading to the identification of specific miRNA signatures for early RTT detection, stratification, disease progression and segregation from other neurodevelopmental disorders. Nevertheless, these data will require verification and validation in further studies with larger sample size including a whole range of ages.
甲基化CpG结合蛋白2（MeCP2）是一种X连锁的表观遗传调节因子，其剂量对神经发育和功能至关重要。MeCP2功能丧失突变会导致雷特综合征（RTT，OMIM #312750），而包含MeCP2和白细胞介素-1受体相关激酶1（IRAK1）的Xq28位点重复会导致MeCP2重复综合征（MDS，OMIM #300260）。这两种都是罕见的神经发育障碍，具有共同的临床症状，包括智力残疾、言语丧失、手部刻板动作、血管舒缩功能障碍和癫痫发作。这项探索性研究的主要目的是确定新的信号通路和潜在的定量生物标志物，以辅助早期诊断和/或在临床试验中监测疾病进展。我们通过RT-PCR分析了20名雷特综合征女性、2名MeCP2重复综合征男性和28名健康对照者的全血基因表达和血浆中的微小RNA（miRNA）表达，并将RNA表达与疾病和临床参数进行了关联分析。我们已经确定了一组用于RTT诊断以及小头畸形和血管舒缩功能障碍患者疾病分层的潜在生物标志物组。我们的研究为开展更大规模的研究奠定了基础，这些研究将有助于识别早期RTT检测、分层、疾病进展以及与其他神经发育障碍区分的特定miRNA特征。然而，这些数据需要在包括所有年龄段的更大样本量的进一步研究中进行验证。
