Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability
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 patie...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1524532/full |
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| author | Baoqiong Liao Baoqiong Liao Wuming Xie Shuwen He |
| author_facet | Baoqiong Liao Baoqiong Liao Wuming Xie Shuwen He |
| author_sort | Baoqiong Liao |
| collection | DOAJ |
| description | 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 3 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. |
| format | Article |
| id | doaj-art-c1f40890ea0646f8bb6aa612e6f163a1 |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-c1f40890ea0646f8bb6aa612e6f163a12025-01-20T05:23:53ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011610.3389/fneur.2025.15245321524532Novel heterozygous ASH1L nonsense variant involved in mild intellectual disabilityBaoqiong Liao0Baoqiong Liao1Wuming Xie2Shuwen He3Ganzhou Maternal and Child Health Hospital, Ganzhou, Jiangxi, ChinaMedical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fuzhou, Fujian, ChinaGanzhou People’s Hospital, Ganzhou, Jiangxi, ChinaDepartment of Chemistry and Molecular Biology, Gothenburg University, Gothenburg, SwedenMutations 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 3 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1524532/fullASH1Lintellectual disabilityonsense mutationWES - whole-exome sequencingneuroscience |
| spellingShingle | Baoqiong Liao Baoqiong Liao Wuming Xie Shuwen He Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability Frontiers in Neurology ASH1L intellectual disability onsense mutation WES - whole-exome sequencing neuroscience |
| title | Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability |
| title_full | Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability |
| title_fullStr | Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability |
| title_full_unstemmed | Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability |
| title_short | Novel heterozygous ASH1L nonsense variant involved in mild intellectual disability |
| title_sort | novel heterozygous ash1l nonsense variant involved in mild intellectual disability |
| topic | ASH1L intellectual disability onsense mutation WES - whole-exome sequencing neuroscience |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1524532/full |
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