{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:42:01Z","timestamp":1776692521939,"version":"3.51.2"},"reference-count":14,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BAPSIS-Cerrahpa\u015fa","award":["TOA-2019-33466"],"award-info":[{"award-number":["TOA-2019-33466"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background\/Objectives: Severe neurodevelopmental disorders caused by homozygous ASTN1 variants have recently been reported. The aim of this study is to present the expanded phenotype and prognostic findings through a longitudinal follow-up of a patient with a homozygous ASTN1 variant. Methods: We conducted a 15-year clinical evaluation of a girl who initially presented at 10 years of age. The genetic etiology was investigated using exome sequencing. Results: The patient had a profound intellectual disability, severe expressive language delay, and infantile-onset epilepsy. She also had microcephaly, achieved independent walking at age 7 and had speech limited to only two words at admission. A novel homozygous frameshift variant, c.2096del (p.Cys699Serfs*22), in ASTN1 was identified. Over the follow-up period, her postnatal microcephaly became more pronounced, and she experienced a late relapse into generalized tonic\u2013clonic seizures after a decade-long remission. She remains entirely dependent on caregivers for basic self-care at age 25. Conclusions: ASTN1-related phenotype is associated with a severe neurodevelopmental disease, and the late relapse of seizures after prolonged remission highlights the need for lifelong neurological monitoring and multidisciplinary care.<\/jats:p>","DOI":"10.3390\/neurolint18040072","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:01:22Z","timestamp":1776686482000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term Follow-Up of a Patient with a Novel Homozygous ASTN1 Variant: A Case Report"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4827-4225","authenticated-orcid":false,"given":"Bu\u015fra","family":"Kasap","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"},{"name":"Institute of Health Sciences, Istanbul University, Istanbul 34126, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilek","family":"Uluda\u011f Alkaya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-3630","authenticated-orcid":false,"given":"Nilay","family":"G\u00fcne\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0190-9139","authenticated-orcid":false,"given":"Salih","family":"T\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bar\u0131\u015f","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beyhan","family":"T\u00fcys\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Cerrahpa\u015fa Medical Faculty, Istanbul University-Cerrahpa\u015fa, Istanbul 34098, Turkey"},{"name":"Department of Pediatrics, Istanbul Atlas University, Istanbul 34408, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.brainresbull.2017.03.003","article-title":"Crosstalk between glia, extracellular matrix and neurons","volume":"136","author":"Song","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/iub.1641","article-title":"Cleave but not leave: Astrotactin proteins in development and disease","volume":"69","author":"Chang","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10556","DOI":"10.1073\/pnas.1811100115","article-title":"N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration","volume":"115","author":"Horn","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1242\/dev.129.4.965","article-title":"Mice that lack astrotactin have slowed neuronal migration","volume":"129","author":"Adams","year":"2002","journal-title":"Development"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.neuron.2015.09.048","article-title":"Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease","volume":"88","author":"Karaca","year":"2015","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/mp.2016.113","article-title":"Clinical Genomics Expands the Morbid Genome of Intellectual Disability and Offers a High Diagnostic Yield","volume":"22","author":"Anazi","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s41431-018-0137-z","article-title":"Comprehensive genomic analysis of patients with disorders of cerebral cortical development","volume":"26","author":"Wiszniewski","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Maddirevula, S., Shamseldin, H.E., Sirr, A., AlAbdi, L., Lo, R.S., Ewida, N., Al-Qahtani, M., Hashem, M., Abdulwahab, F., and Aboyousef, O. (2020). Exploiting the Autozygome to Support Previously Published Mendelian Gene-Disease Associations: An Update. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.580484"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.ajhg.2021.08.009","article-title":"High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population","volume":"108","author":"Mitani","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/cge.14674","article-title":"Homozygous ASTN1 Nonsense Variant Linked to Epileptic Encephalopathy: A Detailed Report with Unique Clinical Presentation","volume":"107","author":"Ayaz","year":"2025","journal-title":"Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ajhg.2025.12.011","article-title":"Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders","volume":"113","author":"Levine","year":"2026","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168967","DOI":"10.1016\/j.jmb.2025.168967","article-title":"AlphaFold Protein Structure Database and 3D-Beacons: New Data and Capabilities","volume":"437","author":"Fleming","year":"2025","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41583-019-0126-4","article-title":"Neuron-glia interactions in the pathophysiology of epilepsy","volume":"20","author":"Patel","year":"2019","journal-title":"Nat. Rev. Neurosci."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/4\/72\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:53:08Z","timestamp":1776689588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/4\/72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,19]]},"references-count":14,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["neurolint18040072"],"URL":"https:\/\/doi.org\/10.3390\/neurolint18040072","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,19]]}}}