Evidence map›Paper›PMID 41035394›Full record

ArticleEpilepsia2025

Haploinsufficiency of brain-specific kinase BRSK1 causes epilepsy and neurodevelopmental disorders.

Qi Zhang, Hiroshi Yamanaka, Ping Li, Yingfeng Li, Tian Luo, Miao Xia, Ting Liu, Xueyan Liu, Qing Lu, Bin Yang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Qi ZhangDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.ORCID https://orcid.org/0000-0002-5440-6837
Hiroshi YamanakaDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Ping LiDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.ORCID https://orcid.org/0009-0000-3505-4533
Yingfeng LiDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Tian LuoDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Miao XiaDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Ting LiuDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Xueyan LiuDepartment of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Qing LuEpilepsy Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Bin YangDepartment of Neurology, Anhui Hospital, Children's Hospital of Fudan University, Hefei, Anhui, China.
Fan HeDepartment of Neurology, Anhui Hospital, Children's Hospital of Fudan University, Hefei, Anhui, China.
Kaixian DuDepartment of Pediatric Neurology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yousheng ShuInstitute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Bo PengInstitute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
Yong-Hui JiangDepartment of Genetics, Neuroscience, and Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Yi WangDepartment of Neurology, Children's Hospital of Fudan University, Shanghai, China.ORCID https://orcid.org/0000-0002-7503-602X

Funding

National Natural Science Foundation of China 82302103Shanghai Municipal Science and Technology 2023SHZDZX02
6 · The paper itself

Abstract

objectiveThe BRSK1 gene encodes brain-specific serine/threonine kinase 1 (also known as SAD-B kinase), which is almost exclusively expressed in the brain and plays critical roles in neuronal polarization, neurotransmitter release, mitochondrial dynamics, and neuronal maturation. This study aimed to investigate the pathogenicity of BRSK1 variants in epilepsy and neurodevelopmental disorders.

methodsTrio-based exome sequencing was performed in 394 probands with epilepsy. Expression analyses and functional validation were conducted using a newly generated Brsk1 exon 4-7 knockout mouse line (Brsk1

resultsSix novel BRSK1 variants were identified in seven probands, including four single nucleotide variants (SNVs) and two indels; five were de novo, one inherited, and one recurrent. Frameshift or nonsense variants led to complete loss of detectable BRSK1 protein, whereas one missense variant reduced protein levels. Both heterozygous and homozygous Brsk1 SIGNIFICANCE: Our genomic and functional studies strongly support BRSK1 haploinsufficiency as a pathogenic mechanism in a human epilepsy syndrome. To our knowledge, this is the first study to implicate the brain-specific serine/threonine kinase BRSK1 in epilepsy and neurodevelopmental disorders.

Indexed as

EpilepsyHaploinsufficiencyNeurodevelopmental DisordersProtein Serine-Threonine KinasesAdolescentAdultAnimalsBrainChildChild, PreschoolExome SequencingFemaleHumansMaleMiceMice, KnockoutProtein Serine-Threonine KinasesBRSK1epilepsyloss of functionneurodevelopmental disorders

Identifiers

PMID41035394
PMCPMC12779330

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.