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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neurogenetics
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1524532

Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability

Provisionally accepted
Liao Baoqiong Liao Baoqiong 1*Wuming Xie Wuming Xie 2Shuwen He Shuwen He 3*
  • 1 Ganzhou Maternal and Child Health Hospital, Ganzhou, China
  • 2 Ganzhou People's Hospital, Ganzhou, Jiangxi Province, China
  • 3 University of Gothenburg, Gothenburg, Västergötland, Sweden

The final, formatted version of the article will be published soon.

    Mutations in ASH1L have been associated with a range of phenotypes, including intellectual disability (ID), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), seizures, as well as differences in skeletal, muscular, and sleep functions. In this study, we describe a patient diagnosed with mild ID, and whole-exome sequencing (WES) of the family identified a novel heterozygous nonsense variant, NM_018489.2: c.2479A>T (p.Lys827*), located in exon 18 of ASH1L, which was predicted to be pathogenic. The nonsense variant in the mild ID patient may disrupt ASH1L function by destabilizing its spatial conformation, leading to decreased activity of the catalytic H3K36 methylation, thereby affecting neurological function. A review of reported ASH1L nonsense mutations to explore genotype-phenotype correlations suggested that these variants typically result in a loss of function. Our findings contribute to understanding the neurodevelopmental pathogenesis of mild ID in patients with the ASH1L nonsense variant mutation.

    Keywords: ASH1L, Intellectual Disability, nonsense mutation, WES - whole-exome sequencing, Neuroscience

    Received: 18 Nov 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Baoqiong, Xie and He. 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:
    Liao Baoqiong, Ganzhou Maternal and Child Health Hospital, Ganzhou, China
    Shuwen He, University of Gothenburg, Gothenburg, 405 30, Västergötland, Sweden

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