{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:23:52Z","timestamp":1789154632854,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of South Australia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Tubulinopathies are associated with malformations of cortical development but not Walker\u2013Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker\u2013Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker\u2013Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the TUBA1A gene (NM_006009.4:c.848A&gt;G; NP_006000.2:p.His283Arg) in the infant, who died at 2 months of age, as the likely cause. We report a previously unpublished, very rare heterozygous TUBA1A mutation with clinical features of macrocephaly and hypoplastic genitalia which have not previously been associated with the gene. The absence of eye phenotypes or mutations in Walker\u2013Warburg-associated genes confirm this as not a new presentation of Walker\u2013Warburg Syndrome but a novel TUBA1A tubulinopathy for neonatologists to be aware of.<\/jats:p>","DOI":"10.3390\/genes15081031","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:45:22Z","timestamp":1722872722000},"page":"1031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker\u2013Warburg-like Features"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-1977","authenticated-orcid":false,"given":"Akzam","family":"Saidin","sequence":"first","affiliation":[{"name":"Epilepsy Research Group, Clinical and Health Sciences, Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia"},{"name":"Novocraft Technologies, Petaling Jaya 46300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-0502","authenticated-orcid":false,"given":"Anet","family":"Papazovska Cherepnalkovski","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Clinic for Gynecology and Obstetrics, Clinical Hospital Center Split, 21000 Split, Croatia"},{"name":"Department of Health Studies, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-7752","authenticated-orcid":false,"given":"Zeeshan","family":"Shaukat","sequence":"additional","affiliation":[{"name":"Epilepsy Research Group, Clinical and Health Sciences, Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todor","family":"Arsov","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, University Goce Delcev in Shtip, 2000 Shtip, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Epilepsy Research Group, Clinical and Health Sciences, Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, Health and Biomedical Innovation, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Bucat","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Clinic for Gynecology and Obstetrics, Clinical Hospital Center Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Cogelja","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Clinic for Gynecology and Obstetrics, Clinical Hospital Center Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-4692","authenticated-orcid":false,"given":"Michael G.","family":"Ricos","sequence":"additional","affiliation":[{"name":"Epilepsy Research Group, Clinical and Health Sciences, Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne M.","family":"Dibbens","sequence":"additional","affiliation":[{"name":"Epilepsy Research Group, Clinical and Health Sciences, Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13023-019-1020-x","article-title":"The mutational and phenotypic spectrum of tuba1a-associated tubulinopathy","volume":"14","author":"Hebebrand","year":"2019","journal-title":"Orphanet J. 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