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Cited by 86Epilepsy research and treatmentGenomics and Rare DiseasesGenetics and Neurodevelopmental Disorders

Novel West syndrome candidate genes in a Chinese cohort

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Peng, Jing, Wang, Ying, He, Fang, Chen, Chen, Wu, Li‐Wen, Yang, Li‐Fen, Ma, Yu‐Ping, Zhang, Wen +6 more·2018·CNS Neuroscience & Therapeutics
DOI 10.1111/cns.12860PMC PMC6489871
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Abstract

Summary: Aims: West syndrome (WS) is a classic form of early infantile epileptic encephalopathy (EIEE) characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on electroencephalography. Genetic defects play a critical role in the pathology of WS, and 54 EIEE genes have been identified till date. This study was designed to uncover new candidate genes for West syndrome. Methods: In this study, we recruited 56 Chinese families with WS of unknown etiology. Whole exome sequencing (WES) was performed to identify Mendelian inheritance rare or novel variants. The association between candidate genes and WS was analyzed from many aspects, including recurrent genes in patients, predicted variant effect on genes, human tolerance to deficient genes, gene expression in the nervous system, coexpression with EIEE genes, mutual interaction with known EIEE proteins, genes related to ion channel or fragile X mental retardation protein function, and mouse models with manifestation of seizures. Genes with supporting evidence from those aspects were defined as highlight candidate genes. Results: Whole exome sequencing identified 112 candidate variants in 89 genes. Among the candidate genes, 33 were autosomal dominant, 22 were autosomal recessive, and 34 were X‐linked. Complex bioinformatic analysis revealed 17 highlight candidate genes: ATP2A2, CD99L2, CLCN6, CYFIP1, CYFIP2, GNB1, GPT2, HUWE1, KMT2D, MYO18A, NOS3, RYR1, RYR2, RYR3, TAF1, TECTA, and UBA1. The majority of highlight candidate genes are calcium‐signaling pathway and mental retardation genes. Conclusions: This is the first WES study of Chinese WS patients with unknown etiology. This combination of phenotypic and genomic data will enable further testing to elucidate mechanisms underlying the pathogenesis of WS.

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  • West syndrome was diagnosed in two individuals with CYFIP2 variants, similar to the reported patient with a CYFIP1 variant.

    “Interestingly, West syndrome was diagnosed in two individuals118, similar to the reported patient with a CYFIP1 variant116.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [116]

    Table 1 lists a CYFIP2 variant in one West syndrome patient (WS1), not two. It also lists a CYFIP1 variant in a separate patient (WS46), but the citing sentence attaches a different citation to that comparison. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • An amino acid in-frame deletion p.Val305del in CYFIP1 was identified in a patient with West syndrome characterized by infantile intellectual disability, epilepsy, and autism spectrum disorder.

    “Furthermore, an amino acid in-frame deletion, p.Val305del, was identified in a patient with West syndrome, who was characterized by infantile ID, epilepsy, and ASD116 (Table 2o).”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [116]

    Table 1 lists a de novo in-frame CYFIP1 deletion in patient WS46 with West syndrome, but records it as c.909_911del, p.303_304del—not p.Val305del. The passages do not establish that this patient had intellectual disability or ASD; the discussion links CYFIP1 to ASD generally, not to WS46’s clinical features. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Peng, J., Wang, Y., He, F., Chen, C., Wu, L., Yang, L., Ma, Y., Zhang, W., Shi, Z., Chen, C., Xia, K., Guo, H., Yin, F., & Pang, N.
Affiliations
  • Xiangya Hospital Central South University (CN)
  • Central South University (CN)
  • Department of Pediatrics Xiangya Hospital Central South University Changsha China
Corresponding author
  • Yin, Fei
  • Pang, Nan
ORCID
Venue
CNS Neuroscience & Therapeutics
Publisher
Wiley
Published
2018-04-17
Volume
24
Issue
12
Pages
1196-1206
ISSN
  • 1755-5930 (ISSN-L)
  • 1755-5949
DOI
10.1111/cns.12860
PMC
PMC6489871
OpenAlex
W2802498898
Cited by
86
References
6
Citations by year
2026: 4 · 2025: 15 · 2024: 14 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 9 · 2019: 9
FWCI
5.71
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • CNS Neuroscience & Therapeutics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (NO. 81701541, NO. 81301031, NO. 81370771, NO. 81371434, NO. 81671297, NO. 81771408, NO. 81771409)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
West syndrome, infantile epileptic encephalopathy, candidate genes, genetic variants, Mendelian inheritance, SERCA2, RyR1, RyR2, RyR3, calcium signaling, FMRP, ion channels, hypsarrhythmia, Chinese patients
MeSH terms
Exome Sequencing, Electroencephalography, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Spasms, Infantile, Cohort Studies, Computational Biology, Calcium Signaling, Genetic Predisposition to Disease, Databases, Genetic, Asian People, Protein Interaction Maps

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