ArticleScientific reports2020
A novel de novo heterozygous DYRK1A mutation causes complete loss of DYRK1A function and developmental delay.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Complex Multifocal Dystonia, Intellectual Disability, and Stereotypies Due to a Novel DYRK1A Variant.Movement disorders clinical practice · 2025Article
- Case Report: Optical genome mapping enables identification of complex balanced chromosomal rearrangements.Frontiers in genetics · 2025Article
- Integrating Genomic Selection and a Genome-Wide Association Study to Improve Days Open in Thai Dairy Holstein Cattle: A Comprehensive Genetic Analysis.Animals : an open access journal from MDPI · 2024Article
- Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability.Journal of autism and developmental disorders · 2024Article
- Discovery of a Novel DYRK1A Mutation (c.524del) in Intellectual Development Disorder Autosomal Dominant 7 (MRD7): A Comprehensive Case Analysis.Case reports in genetics · 2024Article
- Characterizing the autism spectrum phenotype in DYRK1A-related syndrome.Autism research : official journal of the International Society for Autism Research · 2023Article
- CRISPR-based knockout and base editing confirm the role of MYRF in heart development and congenital heart disease.Disease models & mechanisms · 2023Article
- Article
- A Comprehensive Study of De Novo Mutations on the Protein-Protein Interaction Interfaces Provides New Insights into Developmental Delay.Biomolecules · 2022Article
- DYRK1a Inhibitor Mediated Rescue ofFrontiers in pharmacology · 2022Article
- Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Optical genome mapping enables constitutional chromosomal aberration detection.American journal of human genetics · 2021Article
- Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches.International journal of molecular sciences · 2020Article
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Authors and funding
10 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) is essential for human development, and DYRK1A haploinsufficiency is associated with a recognizable developmental syndrome and variable clinical features. Here, we present a patient with DYRK1A haploinsufficiency syndrome, including facial dysmorphism, delayed motor development, cardiovascular system defects, and brain atrophy. Exome sequencing identified a novel de novo heterozygous mutation of the human DYRK1A gene (c.1185dup), which generated a translational termination codon and resulted in a C-terminally truncated protein (DYRK1A-E396ter). To study the molecular effect of this truncation, we generated mammalian cell and Drosophila models that recapitulated the DYRK1A protein truncation. Analysis of the structure and deformation energy of the mutant protein predicted a reduction in protein stability. Experimentally, the mutant protein was efficiently degraded by the ubiquitin-dependent proteasome pathway and was barely detectable in mammalian cells. More importantly, the mutant kinase was intrinsically inactive and had little negative impact on the wild-type protein. Similarly, the mutant protein had a minimal effect on Drosophila phenotypes, confirming its loss-of-function in vivo. Together, our results suggest that the novel heterozygous mutation of DYRK1A resulted in loss-of-function of the kinase activity of DYRK1A and may contribute to the developmental delay observed in the patient.
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