{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T18:47:06Z","timestamp":1768675626835,"version":"3.49.0"},"reference-count":5,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>RNA polymerase III (Pol III)\u2010related leukodystrophies are a group of autosomal recessive neurodegenerative disorders caused by mutations in <jats:italic>POLR3A<\/jats:italic> and <jats:italic>POLR3B<\/jats:italic>. Recently a recessive mutation in <jats:italic>POLR1C<\/jats:italic> causative of Pol III\u2010related leukodystrophies was identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report the case of a Tunisian girl of 14\u00a0years of age who was referred to our department for evaluation of progressive ataxia that began at the age of 5. Genetic diagnosis was performed by NGS and Sanger analysis. In silico predictions were performed using SIFT, PolyPhen\u20102, and Mutation Taster.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neurological examination showed cerebellar and tetrapyramidal syndrome, mixed movement disorders with generalized dystonia and severe myoclonus leading to death at 25\u00a0years. Brain MRI scans showed diffuse hypomyelination associated with cerebellar atrophy. It also showed bilateral T2 hypointensity of the ventrolateral thalamus, part of the posterior limb of the internal capsule, the substantia nigra and the subthalamic nucleus. Next generation sequencing leukodystrophy panel including <jats:italic>POLR3A<\/jats:italic> and <jats:italic>POLR3B<\/jats:italic> was negative. Sanger sequencing of the coding regions of <jats:italic>POLR1C<\/jats:italic> revealed a novel homozygous mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The clinical and imaging findings of patients with <jats:italic>POLR1C<\/jats:italic> hypomyelinating leukodystrophy are reviewed. Interestingly, severe myoclonic dystonia and T2 hypointensity of the substantia nigra and the subthalamic nucleus are not reported yet and could be helpful for the diagnosis of <jats:italic>POLR1C<\/jats:italic> hypomyelinating leukodystrophy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.914","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T03:53:35Z","timestamp":1564631615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel <i>POLR1C<\/i> mutation in RNA polymerase III\u2010related leukodystrophy with severe myoclonus and dystonia"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5662","authenticated-orcid":false,"given":"Ichraf","family":"Kraoua","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Neurology, LR18SP04, National Institute Mongi Ben Hmida of Neurology University of Tunis El Manar Tunis Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adnane","family":"Karkar","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology Laboratory, Medical School of Casablanca Hassan II University Casablanca Morocco"},{"name":"INSERM UMR1141, Sorbonne Paris Cit\u00e9, DHU PROTECT, Paris Diderot University Robert Debr\u00e9 Hospital Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrine","family":"Drissi","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanene","family":"Benrhouma","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Neurology, LR18SP04, National Institute Mongi Ben Hmida of Neurology University of Tunis El Manar Tunis 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France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Elmaleh","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Robert Debr\u00e9 Hospital Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Ben Hamouda","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, LR11IPT05, Pasteur Institute of Tunisia University of Tunis El Manar Tunis Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odile","family":"Boespflug\u2010Tanguy","sequence":"additional","affiliation":[{"name":"INSERM UMR1141, Sorbonne Paris Cit\u00e9, DHU PROTECT, Paris Diderot University Robert Debr\u00e9 Hospital Paris France"},{"name":"Department of Neuropediatrics and Metabolic Diseases, Reference Center for Leukodystrophies Robert Debr\u00e9 Hospital, AP\u2010HP Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilfghem","family":"Ben Youssef\u2010Turki","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Neurology, LR18SP04, National Institute Mongi Ben Hmida of Neurology University of Tunis El Manar Tunis Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imen","family":"Dorboz","sequence":"additional","affiliation":[{"name":"INSERM UMR1141, Sorbonne Paris Cit\u00e9, DHU PROTECT, Paris Diderot University Robert Debr\u00e9 Hospital Paris 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