About this Research Topic
DYRK1A Syndrome is a recognizable clinical phenotype caused by de novo mutations in the DYRK1A gene and is one of the most frequent monogenic neurodevelopmental disorders (affecting around 0.3% to 0.5% of individuals). The DYRK1A gene encodes the dual-specificity tyrosine phosphorylation-regulated kinase 1A protein, which is critical for development of the central nervous system and a key regulator of neurogenesis, neuronal differentiation, migration, and proliferation. The majority of variants associated with DYRK1A syndrome occur in the catalytic and kinase domains and have a loss of function effect resulting in DYRK1A haploinsufficiency; however, variants outside of these regions have also been described as pathogenic. A key area of research remains to better understand the consequences of variants within DYRK1A Syndrome on protein levels and function both in in vitro and in vivo models, and the need to identify potential genotype-phenotype relationships. DYRK1A Syndrome has no therapeutic options, and identifying promising novel approaches for treatment is the highest research priority.
The goal of this research topic is to advance DYRK1A Syndrome through the following:
1) Underlying Mechanisms: There is a need to understand the functional consequences of DYRK1A haploinsufficiency mutations on mRNA, protein, and function in in vitro and in vivo models. Furthermore, there is a critical need to assess how the functional consequences of mutations may lead to differences in clinical phenotypes through development of genotype-phenotype relationships.
2) Disease models: There is a need to model the neurodevelopmental impact of DYRK1A mutations using patient-derived IPSCs and animal models to characterize the DYRK1A Syndrome phenotype. These in vivo and in vitro phenotypes will be used to determine efficacy of DYRK1A haploinsufficiency rescue. Additionally, the development of reliable biomarkers (imaging, blood, tissue, etc.) to measure and monitor DYRK1A activity in vivo, for application in patients, is of special interest.
3) Therapeutics: There is an unmet need for disease modifying treatments in DYRK1A syndrome since no therapy exists today. We are interested in the use of novel precision medicines or targeted therapies that improve and/or correct DYRK1A haploinsufficiency. There is special interest in evaluating therapeutics in animal models; however, in vitro studies will also be considered.
4) Clinical Presentations: There is limited data on the clinical manifestations and natural history of DYRK1A Syndrome. Submissions of clinical relevance on the phenotypic spectrum of patients with defined mutations in DYRK1A Syndrome including older individuals is of importance.
We welcome contributions of original research, reviews, perspectives, and case reports.
The goal of this research topic is to advance DYRK1A Syndrome through the following:
1) Underlying Mechanisms: There is a need to understand the functional consequences of DYRK1A haploinsufficiency mutations on mRNA, protein, and function in in vitro and in vivo models. Furthermore, there is a critical need to assess how the functional consequences of mutations may lead to differences in clinical phenotypes through development of genotype-phenotype relationships.
2) Disease models: There is a need to model the neurodevelopmental impact of DYRK1A mutations using patient-derived IPSCs and animal models to characterize the DYRK1A Syndrome phenotype. These in vivo and in vitro phenotypes will be used to determine efficacy of DYRK1A haploinsufficiency rescue. Additionally, the development of reliable biomarkers (imaging, blood, tissue, etc.) to measure and monitor DYRK1A activity in vivo, for application in patients, is of special interest.
3) Therapeutics: There is an unmet need for disease modifying treatments in DYRK1A syndrome since no therapy exists today. We are interested in the use of novel precision medicines or targeted therapies that improve and/or correct DYRK1A haploinsufficiency. There is special interest in evaluating therapeutics in animal models; however, in vitro studies will also be considered.
4) Clinical Presentations: There is limited data on the clinical manifestations and natural history of DYRK1A Syndrome. Submissions of clinical relevance on the phenotypic spectrum of patients with defined mutations in DYRK1A Syndrome including older individuals is of importance.
We welcome contributions of original research, reviews, perspectives, and case reports.
Keywords: DYRK1A, DYRK1A Syndrome, Neurodevelopment, Therapeutics, Clinical Presentations, Disease Models, Disease Mechanisms
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
