Research Explained: Identification of Novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature re

Authors: Ruo-Hao Wu, Wen-ting Tang, Kun-yin Qiu, Xiao-juan Li, Dan-xia Tang, Zhe Meng, Zhan-wen He

Publication Date: May 26, 2021

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

Link to article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161887/

Research Explained Summary:

This case report profiles two new OCNDS patients, then expands to broadly review the literature of all reported OCNDS patients to identify potential correlations between each patient’s specific genetic mutations and any symptoms they experience. 

The first patient arrived at the clinic at age 3 with severe growth retardation and recurrent febrile seizures. Her development in terms of movement and speaking occurred at a normal pace, but she had her first febrile seizure at nine months of age, experiencing a total of five episodes. All the seizures went away on their own and didn’t require treatment. During her initial consultation, other reported abnormalities included a smaller than usual pituitary gland (a gland which regulates most hormones in the body), and mild immunodeficiency. The second patient arrived at the clinic at age 2, also with major growth delay. This patient’s developmental milestones were severely delayed – she could not yet sit, stand, or speak. However, unlike the first patient, she had a perfectly functioning immune system.

Genetic testing was performed on both patients, finding mutations in the CSNK2A1 gene. Each patient had a different mutation, with the first patient having p.H160R, while the second had p.R80C. Both mutations were predicted to be the major cause of their symptoms. A full search of the OCNDS literature revealed 35 patients with detailed workups. The authors tried to link specific mutations found in CSNK2A1 to specific manifestations of OCNDS. The only connection they were able to find was mutations in a specific domain of the CSNK2A1 gene known as the “ATP/GTP binding-loop" were more likely to lead to multi-organ abnormalities, although these symptoms weren’t necessarily more severe. This study further illustrates the wide variety of manifestations of OCNDS and confirms the lack of a strong correlation between what mutation a patient has with their symptoms.