Sozańska Nikola, Krupnik Viktoryia, Greb-Markiewicz Beata, Ożyhar Andrzej, Tarczewska Aneta
Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, Wroclaw, 50-370, Poland.
Cell Commun Signal. 2025 Jun 1;23(1):258. doi: 10.1186/s12964-025-02265-1.
Pitt-Hopkins Syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations in the TCF4 gene (18q21.2), encoding the transcription factor 4 (TCF4). This protein is critical for central nervous system development and neuronal maturation. Mutations in TCF4, which range from point mutations to large deletions, result in varying clinical severity, including intellectual disability (ID), motor impairments, and autistic features. Despite its rarity, PTHS has gained increasing attention due to advances in understanding the genetic and molecular mechanisms underlying TCF4 function. Recent research has enhanced diagnostic approaches, including genetic testing techniques like genome sequencing, enabling more accurate identification of the disorder. Despite the evident enhancement in the PTHS management from a medical standpoint, the molecular underpinnings of the disorder progression remain puzzling. This is particularly the case where the disease is caused by point mutations. This review summarizes the latest findings on TCF4 function in PTHS, discusses the variability in mutation effects, highlights current diagnostic and therapeutic advancements, and attempts to explain the molecular bases of mutated TCF4 malfunctionality.
皮特-霍普金斯综合征（PTHS）是一种罕见的神经发育障碍，由位于18q21.2的TCF4基因发生突变引起，该基因编码转录因子4（TCF4）。这种蛋白质对中枢神经系统发育和神经元成熟至关重要。TCF4基因的突变范围从点突变到大片段缺失，导致不同的临床严重程度，包括智力残疾（ID）、运动障碍和自闭症特征。尽管PTHS很罕见，但由于在理解TCF4功能的遗传和分子机制方面取得了进展，它越来越受到关注。最近的研究改进了诊断方法，包括基因组测序等基因检测技术，能够更准确地识别这种疾病。尽管从医学角度来看，PTHS的管理有了明显改善，但该疾病进展的分子基础仍然令人困惑。在由点突变引起的疾病中尤其如此。这篇综述总结了关于PTHS中TCF4功能的最新发现，讨论了突变效应的变异性，强调了当前的诊断和治疗进展，并试图解释突变的TCF4功能异常的分子基础。
