REVIEW article
Front. Neurol.
Sec. Neurogenetics
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1664776
Clinical Characteristics, Molecular Mechanisms, and Exploration of Association with Gastrointestinal Symptoms in CHAMP1 Gene Variation-Related Neurodevelopmental Disorders
Provisionally accepted- 1Henan University of Chinese Medicine, Zhengzhou, China
- 2Changchun University of Chinese Medicine, Changchun, China
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The CHAMP1 (Chromosome Alignment-Maintaining Phosphoprotein 1) gene encodes a nuclear protein crucial for maintaining proper chromosome alignment and genomic stability during cell mitosis. Heterozygous variants of this gene, particularly de novo truncating mutations, are the primary cause of a rare neurodevelopmental disorder: autosomal dominant intellectual disability Autosomal Dominant Mental Retardation 40 (MRD40 )or CHAMP1-related Neurodevelopmental Disorder(CHAND). The core clinical features of this disorder include moderate to severe global developmental delay, intellectual disability, significant language impairment, and distinctive facial features. Additionally, patients may exhibit abnormal muscle tone, behavioral issues (such as autism spectrum disorder traits and attention deficit hyperactivity disorder), epilepsy, microcephaly, and involvement of other multi-systemic complications, including gastrointestinal dysfunction. The pathogenic mechanisms of CHAMP1 truncating mutations remain debated, with main hypotheses including haploinsufficiency and dominant-negative effect or gain-of-function, where the latter better explains the more severe clinical phenotypes observed in some patients. Although neurological manifestations are the research focus of CHAMP1-related disorders, the involvement of other systems such as the digestive system—particularly symptoms like repeated vomiting—has been underreported and lacks systematic research within this disease spectrum. This review aims to integrate the latest research progress on the molecular functions of the CHAMP1 gene, the pathogenic mechanisms of its variants, and the clinical phenotype spectrum of related neurodevelopmental disorders. Based on clinical observations, we also preliminarily explored the potential association between CHAMP1 gene variation and gastrointestinal symptoms (especially recurrent vomiting), with the goal of providing valuable references for clinical diagnosis, management, and future research directions for this rare disease.
Keywords: CHAMP1 Gene, CHAND, Truncating mutation, developmental delay, Gastrointestinal symptoms, Haploinsufficiency, Dominant-negative effect, Kinetochore-microtubuleattachment
Received: 16 Jul 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Xu, Tao, Chen, Dong and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guojuan Dong, donggj@ccucm.edu.cn
Yan Xu, superxy@hactcm.edu.cn
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