{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:10:41Z","timestamp":1789827041123,"version":"4.0.1"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development Institute (KHIDI)","award":["RS-2023-00267049"],"award-info":[{"award-number":["RS-2023-00267049"]}]},{"name":"Korea Health Industry Development Institute (KHIDI)","award":["2025-0018"],"award-info":[{"award-number":["2025-0018"]}]},{"name":"Soonchunhyang University Research Fund","award":["RS-2023-00267049"],"award-info":[{"award-number":["RS-2023-00267049"]}]},{"name":"Soonchunhyang University Research Fund","award":["2025-0018"],"award-info":[{"award-number":["2025-0018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Spectrin proteins are critical cytoskeleton components that maintain cellular structure and mediate intracellular transport. Pathogenic variants in SPTBN1, encoding \u03b2II-spectrin, have been associated with various neurodevelopmental disorders, including developmental delay, intellectual disability, autism spectrum disorder, and epilepsy. Here we report a Korean infant with infantile epileptic spasms syndrome (IESS) and an SPTBN1 mutation and provide a review of this mutation. Methods: The genomic data of the patient were analyzed by whole exome sequencing. A comprehensive literature review was conducted to identify and analyze all reported SPTBN1 variants, resulting in a dataset of 60 unique mutations associated with neurodevelopmental phenotypes. Case Presentation: A 10-month-old Korean female presented with IESS associated with a de novo heterozygous SPTBN1 mutation (c.785A&gt;T; p.Asp262Val). The patient exhibited global developmental delay, microcephaly, hypotonia, spasticity, and MRI findings of diffuse cerebral atrophy and corpus callosum hypoplasia. Electroencephalography revealed hypsarrhythmia, confirming the diagnosis of IESS. Seizures persisted despite initial treatment with vigabatrin and steroids. Genetic analysis identified a likely pathogenic variant within the calponin homology 2 (CH2) domain of SPTBN1. Conclusions: This is the first report of an association between IESS and an SPTBN1 CH2 domain mutation in a Korean infant. This finding expands the clinical spectrum of SPTBN1-related disorders and suggests domain-specific effects may critically influence phenotypic severity. Further functional studies are warranted to elucidate the pathogenic mechanisms of domain-specific variants.<\/jats:p>","DOI":"10.3390\/genes16080904","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T10:25:34Z","timestamp":1753784734000},"page":"904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Case of Infantile Epileptic Spasms Syndrome with the SPTBN1 Mutation and Review of \u03b2II-Spectrin Variants"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-6946","authenticated-orcid":false,"given":"Han Na","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea"},{"name":"Department of Pediatrics, College of Medicine, Kyung-Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8196-5985","authenticated-orcid":false,"given":"Juyeon","family":"Ryu","sequence":"additional","affiliation":[{"name":"College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4276-9777","authenticated-orcid":false,"given":"Seung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0235-5318","authenticated-orcid":false,"given":"Jin-Hwa","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liem, R.K. (2016). Cytoskeletal Integrators: The Spectrin Superfamily. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a018259"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41583-022-00674-6","article-title":"Spectrins: Molecular organizers and targets of neurological disorders","volume":"24","author":"Lorenzo","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/s41588-021-00886-z","article-title":"Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome","volume":"53","author":"Cousin","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature13908","article-title":"The contribution of de novo coding mutations to autism spectrum disorder","volume":"515","author":"Iossifov","year":"2014","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Snyder, H.E., Jain, P., RamachandranNair, R., Jones, K.C., and Whitney, R. (2024). Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine. Genes, 15.","DOI":"10.3390\/genes15030266"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/jhg.2015.5","article-title":"SPTAN1 encephalopathy: Distinct phenotypes and genotypes","volume":"60","author":"Tohyama","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.ajhg.2018.04.012","article-title":"\u03b2IV Spectrinopathies Cause Profound Intellectual Disability, Congenital Hypotonia, and Motor Axonal Neuropathy","volume":"102","author":"Wang","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ng1728","article-title":"Spectrin mutations cause spinocerebellar ataxia type 5","volume":"38","author":"Ikeda","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1126\/science.1232251","article-title":"Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons","volume":"339","author":"Xu","year":"2013","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15686","DOI":"10.1073\/pnas.1820649116","article-title":"\u03b2II-spectrin promotes mouse brain connectivity through stabilizing axonal plasma membranes and enabling axonal organelle transport","volume":"116","author":"Lorenzo","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2215632120","DOI":"10.1073\/pnas.2215632120","article-title":"The contributions of rare inherited and polygenic risk to ASD in multiplex families","volume":"120","author":"Cirnigliaro","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e63851","DOI":"10.1002\/ajmg.a.63851","article-title":"Diverse clinical presentation of SPTBN1 variants: Complex versus primary attention-deficit\/hyperactivity disorder","volume":"197","author":"Harstad","year":"2025","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sandoval-Talamantes, A.K., Tenorio-Casta\u00f1o, J.A., Santos-Simarro, F., Ad\u00e1n, C., Fern\u00e1ndez-Elvira, M., Garc\u00eda-Fern\u00e1ndez, L., Mu\u00f1oz, Y., Lapunzina, P., and Nevado, J. (2023). NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital. Genes, 14.","DOI":"10.3390\/genes14112091"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1038\/s41588-024-01836-1","article-title":"Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings","volume":"56","author":"Schmidt","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41525-022-00284-2","article-title":"Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants","volume":"7","author":"Tuncay","year":"2022","journal-title":"NPJ Genom. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Woodbury-Smith, M., Lamoureux, S., Begum, G., Nassir, N., Akter, H., O\u2019Rielly, D.D., Rahman, P., Wintle, R.F., Scherer, S.W., and Uddin, M. (2022). Mutational Landscape of Autism Spectrum Disorder Brain Tissue. Genes, 13.","DOI":"10.3390\/genes13020207"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s13023-024-03214-w","article-title":"Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing","volume":"19","author":"Wu","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41588-022-01148-2","article-title":"Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.neuron.2017.04.024","article-title":"De Novo Coding Variants Are Strongly Associated with Tourette Disorder","volume":"94","author":"Willsey","year":"2017","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/ajmg.a.62201","article-title":"Heterozygous variants in SPTBN1 cause intellectual disability and autism","volume":"185","author":"Rosenfeld","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.ajhg.2010.04.013","article-title":"Dominant-negative mutations in alpha-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay","volume":"86","author":"Saitsu","year":"2010","journal-title":"Am. J. Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/904\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:57Z","timestamp":1760033877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":23,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["genes16080904"],"URL":"https:\/\/doi.org\/10.3390\/genes16080904","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]}}}