{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:02:31Z","timestamp":1778544151605,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>POLIII\u2010related leukodystrophies are a group of recently recognized hereditary white matter diseases with a similar clinical and radiological phenotype. No Tunisian studies have been published about POLIII\u2010related leukodystrophy due to <jats:italic>POLR3A<\/jats:italic> variants. The aim of this study was to contribute to the clinical, radiological, and genetic characterization of <jats:italic>POLR3A<\/jats:italic>\u2010related leukodystrophy in a Tunisian cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report six cases of genetically confirmed <jats:italic>POLR3A<\/jats:italic>\u2010related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15\u2009months and 6\u2009years.<\/jats:p><jats:p>The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients.<\/jats:p><jats:p>Molecular analysis identified the same bi\u2010allelic NM_007055.4:c.2011T&gt;C; p.(Trp671Arg) variant in the <jats:italic>POLR3A<\/jats:italic> gene in all patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian <jats:italic>POLR3A<\/jats:italic> patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70007","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T16:40:31Z","timestamp":1729615231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent <scp>POLR3A<\/scp> Mutation in Six Unrelated Tunisian Families"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5662","authenticated-orcid":false,"given":"Ichraf","family":"Kraoua","sequence":"first","affiliation":[{"name":"LR18SP04, Department of Child and Adolescent Neurology Faculty of Medicine of Tunis, National Institute Mongi Ben Hmida of Neurology, University of Tunis El Manar  Tunis 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