Genotype-Phenotype Correlation in a Patient with Pathogenic Variant in CDK13 Gene

Background: CDK13 (cyclin-dependent kinase 13) is one of the 21 humancyclin-dependent kinases. It is involved in phosphorylation of RNA polymerase II and it is associated with various biological processes including transcriptional regulation, alternative splicing of mRNA and axonal elongation. To date, constitutional mutations in five cyclin-dependent kinases (CDK4, CDK5, CDK6, CDK10 and CDK13) have been associated with human phenotypes, and only 44 patients with a mutation in CDK13 gene were presented in the literature. Most of them had characteristic craniofacial features, feeding difficulties in infancy, and structural malformations of heart or brain.

Our aim is to discuss the case of a patient with de novo frameshift mutation in CDK13 gene.
Methods: Molecular analysis showed de novo heterozygous frameshift mutation p.Ala162GlyfsTer108 in CDK13 gene. The genetic analysis was performed by whole-exome sequencing. The library was prepared using Agilent Sureselect VI exome Kit and analyzed with a NovaSeq sequencing platform. The presence of the detected genetic variant was confirmed by Sanger sequencing.

Results: Our patient was born at 32 weeks of gestation by cesarian section, together with her healthy twin, of healthy, nonconsanguineous parents. S. Our patients’ birth weight was 1825g, length- 43 cm, OFC-29 cm. In the fifth day she was diagnosed with microcolon. She was fed by parenteral feeding till she was 5. Cranial ultrasound after birth did not show any abnormalities. Echocardiography from that period revealed: patent ductus arteriosus (PDA), patent foramen ovale (PFO), I/IIotricuspid regurgitation.
At the age of 9 the girl was admitted to our Genetic Clinic. Among her main health problems were: short stature, dysmorphic features, intellectual disability.

Conclusion:The case of our patient is yet another contribution to the study of the role of CDK13 gene and the symptoms which occur as a result of its’ mutation.