Case report: A novel frameshift mutation in BRSK2 causes autism in a 16-year old Chinese boy

Yu Hu; Miao Li; Yanmei Shen; Tianyun Wang; Qiwei Liu; Zhonghua Lu; Hong Wang; Xuerong Luo; Lixin Yang

doi:10.3389/fpsyt.2023.1205204

Case report: A novel frameshift mutation in BRSK2 causes autism in a 16-year old Chinese boy

Front Psychiatry. 2023 Aug 21:14:1205204. doi: 10.3389/fpsyt.2023.1205204. eCollection 2023.

Authors

Yu Hu^#^{1

2}, Miao Li^#^{1

2}, Yanmei Shen^#³, Tianyun Wang^{4

5

6

7}, Qiwei Liu^{1

2

8}, Zhonghua Lu^{1

2}, Hong Wang^{1

2}, Xuerong Luo³, Lixin Yang^{1

2}

Affiliations

¹ The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
² Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.
³ Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁴ Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
⁵ Neuroscience Research Institute, Peking University, Beijing, China.
⁶ Key Laboratory for Neuroscience, Ministry of Education of China and National Health Commission of China, Beijing, China.
⁷ Autism Research Center, Peking University Health Science Center, Beijing, China.
⁸ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China.

^# Contributed equally.

Abstract

Serine/threonine protein kinases are involved in axon formation and neuronal polarization and have recently been implicated in autism spectrum disorder (ASD) and neurodevelopmental disorders (NDD). Here, we focus on BRSK2, which encodes brain-specific serine/threonine protein kinase 2. Although previous studies have reported 19 unrelated patients with BRSK2 pathogenic variation, only 15 of 19 patients have detailed clinical data. Therefore, more case reports are needed to enrich the phenotype associated with BRSK2 mutations. In this study, we report a novel de novo frameshift variant (c.442del, p.L148Cfs^*39) identified by exome sequencing in a 16 year-old Chinese boy with ASD. The proband presented with attention-deficit, auditory hallucinations, limb tremor, and abnormal brain electrical activity mapping. This study expands the phenotypic spectrum of BRSK2-related cases and reveals the highly variable severity of disorders associated with BRSK2.

Keywords: BRSK2; autism; clinical phenotype; de novo mutation; exome sequence.

Publication types

Case Reports

Grants and funding

This work was supported by research grants from the National Natural Science Foundation of China (NSFC, No. 32000728 and NSFC-Guangdong Joint Fund-U20A6005), Shenzhen Science and Technology Program (JCYJ20220818101608018), and supported, in part, by the Fundamental Research Funds for the Central Universities starting fund (BMU2022RCZX038) and grant from the NSFC (No. 82201314) to TW.