There are 21 human cyclin-dependent kinases which are involved in regulation of the cell cycle, transcription, RNA splicing, apoptosis and neurogenesis. Five of them: CDK4, CDK5, CDK6, CDK10 and CDK13 are associated with human phenotypes. To date, only 62 patients have been presented with mutated CDK13 gene. Those patients had developmental delay, dysmorphic facial features, feeding difficulties, different structural heart and brain defects. 36 of them had missense mutation affecting the protein kinase domain of CDK13. Our patient is the first person reported so far with a frameshift mutation which introduce premature stop codon in the first exon of the CDK13 gene. She has symptoms characteristic for congenital heart defects, facial dysmorphism and intellectual developmental disorder (CHDFIDD).

BACKGROUND: It is not uncommon that an infant with a disease of unknown etiology is presented to a physician. Facial dysmorphic features lead to a different diagnosis. It is a challenge to link the presentation to the newfound diagnosis.
METHODS: A 37-day-old Yemenite Jewish girl was presented to our institution with a clinical picture of pseudohypoaldosteronism due to abnormal facial features and a psychomotor developmental delay. Further investigation led to the diagnosis of CDK13-related disorder. According to the literature, CDK13 has a key role in the cell cycle, but no interference with the aldosterone signaling pathway or electrolyte balance was described. No mutations in the previously described gene NR3C2 (cytogenetic location 4q31.23), encoding the mineralocorticoid receptor, were found. Although the clinical presentation corresponded to pseudohypoaldosteronism type 1, we could not genetically confirm this.
CONCLUSIONS: Probably pseudohypoaldosteronism was a coincidental finding in this girl with a CDK13 mutation, but because only limited information is known about CDK13-related disorders, further investigation could be more informative to clarify this presentation.

De novo variants in the gene encoding cyclin-dependent kinase 13 (CDK13) have been associated with congenital heart defects and intellectual disability (ID). Here, we present the clinical assessment of 15 individuals and report novel de novo missense variants within the kinase domain of CDK13. Furthermore, we describe 2 nonsense variants and a recurrent frame-shift variant. We demonstrate the synthesis of 2 aberrant CDK13 transcripts in lymphoblastoid cells from an individual with a splice-site variant. Clinical characteristics of the individuals include mild to severe ID, developmental delay, behavioral problems, (neonatal) hypotonia and a variety of facial dysmorphism. Congenital heart defects were present in 2 individuals of the current cohort, but in at least 42% of all known individuals. An overview of all published cases is provided and does not demonstrate an obvious genotype-phenotype correlation, although 2 individuals harboring a stop codons at the end of the kinase domain might have a milder phenotype. Overall, there seems not to be a clinically recognizable facial appearance. The variability in the phenotypes impedes an à vue diagnosis of this syndrome and therefore genome-wide or gene-panel driven genetic testing is needed. Based on this overview, we provide suggestions for clinical work-up and management of this recently described ID syndrome.

Cyclin dependent kinases (CDKs) are a family of proteins involved in the regulation of cell cycle progression and attractive targets in oncology. The regulation of CDKs activities is achieved by their association with cyclin partners and kinases, phosphatases and specific inhibitors. Different CDKs complexes exert their functions at different phases. CDK1 is a master modulator in the initiation and transition process through mitosis of the cell cycle. Previous studies have shown that loss of CDK1 activity or the aberrant expression of CDK1 involved in G2 phase arrest and many tumor types, thereby validating CDK1 as a therapeutic target. Therefore, a surge of interest has been devoted to searching for potent CDK1 inhibitors as effective chemotherapeutic agents. Herein we focus, in this review, mainly on the studies about the structure, functions and different structure classes of potent CDK1 inhibitors.

For development to proceed normally, animal eggs must undergo a maturation process that ultimately depends on phosphorylations of key regulatory proteins. To analyze the kinases that mediate these phosphorylations, eggs of marine nemertean worms have been treated with pharmacological modulators of intracellular signaling pathways and subsequently probed with immunoblots employing phospho-specific antibodies. This article both reviews such analyses and compares them with those conducted on mammals, while focusing on how egg maturation in nemerteans is affected by signaling pathways involving cAMP, mitogen-activated protein kinases, Src-family kinases, protein kinase C isotypes, AMP-activated kinase, and the Cdc2 kinase of maturation-promoting factor.