Research Explained: A novel de novo mutation in CSNK2A1: reinforcing the link to neurodevelopmental abnormalities and dysmorphic features

Authors: Joanne Trinh, Irina Hϋning, Nadja Budler, Volker Hingst, Katja Lohmann, Gabrielle Gillessen-Kaesbach.

Publication Date: July 20, 2017

Research Explained By: Brad Davidson, CSNK2A1 Foundation Science Communication Intern

Link to article: https://www.nature.com/articles/jhg201773

Research Explained Summary:

This case report identifies and describes a 7-year-old German boy with OCNDS. At birth, doctors suspected a neurodevelopmental disorder, initially anticipating Down syndrome. Microcephaly (small head/brain) became an obvious sign as the child grew, and motor and speech development were delayed to 2 and 3 years of age respectively. At the last check-up reported, microcephaly and global developmental and intellectual delays were still apparent. Sleep disturbances and hyperactive behavior were reported by the parents, and diagnostic tests showed that the patient underperformed in terms of social responsiveness and sensorimotor function, among other categories. 

These symptoms elicited genetic testing of the patient and his unaffected parents. Two novel and potentially causative mutations were found, one in the CSNK2A1 gene and one in the STAT2 gene. Both mutations were de novo, or only present in the patient, indicating this might be what differentiated the parents from their atypically developing son. At the time, STAT2 was known to biologically be involved in neurologic processes, although these studies were not confirmed in human patients. However, the CSNK2A1 gene had just been discovered as the causative gene for OCNDS, leading to an OCNDS diagnosis. This case report continued to illustrate the vast number of manifestations OCNDS can cause in different patients.