{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:08:46Z","timestamp":1787861326029,"version":"build-2784847793"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Fujian Province Medical Innovation Foundation","award":["2021CXB001"],"award-info":[{"award-number":["2021CXB001"]}]},{"name":"Fujian Province Medical Innovation Foundation","award":["2022CXB002"],"award-info":[{"award-number":["2022CXB002"]}]},{"name":"Fujian Province Medical Innovation Foundation","award":["2022CXA001"],"award-info":[{"award-number":["2022CXA001"]}]},{"name":"Fujian Province Medical Innovation Foundation","award":["2022CXB002"],"award-info":[{"award-number":["2022CXB002"]}]},{"name":"Fujian Province Medical Innovation Foundation","award":["2021CXB001"],"award-info":[{"award-number":["2021CXB001"]}]},{"name":"Fujian Province Medical Innovation Foundation","award":["2022CXA001"],"award-info":[{"award-number":["2022CXA001"]}]},{"name":"the Special Research Foundation of Fujian Provincial Department of Finance , China","award":["2020-822"],"award-info":[{"award-number":["2020-822"]}]},{"name":"the Special Research Foundation of Fujian Provincial Department of Finance , China","award":["2021-848"],"award-info":[{"award-number":["2021-848"]}]},{"name":"the Special Research Foundation of Fujian Provincial Department of Finance , China","award":["2022-840"],"award-info":[{"award-number":["2022-840"]}]},{"name":"Fujian Province Natural Science Fund Project","award":["2022J01996"],"award-info":[{"award-number":["2022J01996"]}]},{"name":"Fujian Province Natural Science Fund Project","award":["2021J02053"],"award-info":[{"award-number":["2021J02053"]}]},{"name":"Fujian Province Natural Science Fund Project","award":["2021J01704"],"award-info":[{"award-number":["2021J01704"]}]},{"name":"Joint Funds for the innovation of science and Technology in Fujian province","award":["2023Y9284"],"award-info":[{"award-number":["2023Y9284"]}]},{"name":"National famous and old Chinese medicine experts (Zhang Xuemei, Yan Xiaohua) inheritance studio construction project"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by <jats:italic>POLR3A<\/jats:italic> mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the <jats:italic>POLR3A<\/jats:italic> (NM_007055.4) gene c. 2300G\u2009&gt;\u2009T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed <jats:italic>POLR3A<\/jats:italic> wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (<jats:italic>POLR3A<\/jats:italic>, <jats:italic>BC200<\/jats:italic>, and tRNA Leu-CAA expression decreased), and <jats:italic>MBP<\/jats:italic> and 18S rRNA expressions were decreased. This study indicates that the <jats:italic>POLR3A<\/jats:italic> p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.<\/jats:p>","DOI":"10.1038\/s41598-024-58452-6","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T09:13:50Z","timestamp":1711962830000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation"],"prefix":"10.1038","volume":"14","author":[{"given":"Dan-dan","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-lin","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo\u2011li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-fu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-wu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-wei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"58452_CR1","doi-asserted-by":"publisher","first-page":"7623","DOI":"10.1038\/ncomms8623","volume":"6","author":"I Thiffault","year":"2015","unstructured":"Thiffault, I. et al. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. Nat. Commun. 6, 7623. https:\/\/doi.org\/10.1038\/ncomms8623 (2015).","journal-title":"Nat. Commun."},{"key":"58452_CR2","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1212\/01.wnl.0000343049.00540.c8","volume":"72","author":"R Schiffmann","year":"2009","unstructured":"Schiffmann, R. & van der Knaap, M. S. Invited article: An MRI-based approach to the diagnosis of white matter disorders. Neurology 72, 750\u2013759. https:\/\/doi.org\/10.1212\/01.wnl.0000343049.00540.c8 (2009).","journal-title":"Neurology"},{"key":"58452_CR3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/mdc3.12715","volume":"6","author":"G Al Yazidi","year":"2019","unstructured":"Al Yazidi, G. et al. Dystonia in RNA polymerase III-related leukodystrophy. Mov. Disord. Clin. Pract. 6, 155\u2013159. https:\/\/doi.org\/10.1002\/mdc3.12715 (2019).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"58452_CR4","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1007\/s10072-021-05462-1","volume":"43","author":"I Di Donato","year":"2022","unstructured":"Di Donato, I. et al. POLR3A variants in hereditary spastic paraparesis and ataxia: Clinical, genetic, and neuroradiological findings in a cohort of Italian patients. Neurol. Sci. 43, 1071\u20131077. https:\/\/doi.org\/10.1007\/s10072-021-05462-1 (2022).","journal-title":"Neurol. Sci."},{"key":"58452_CR5","doi-asserted-by":"publisher","first-page":"631802","DOI":"10.3389\/fncel.2020.631802","volume":"14","author":"S Perrier","year":"2020","unstructured":"Perrier, S., Michell-Robinson, M. A. & Bernard, G. POLR3-related leukodystrophy: Exploring potential therapeutic approaches. Front. Cell. Neurosci. 14, 631802. https:\/\/doi.org\/10.3389\/fncel.2020.631802 (2020).","journal-title":"Front. Cell. Neurosci."},{"key":"58452_CR6","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.tig.2007.09.001","volume":"23","author":"G Dieci","year":"2007","unstructured":"Dieci, G., Fiorino, G., Castelnuovo, M., Teichmann, M. & Pagano, A. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614\u2013622. https:\/\/doi.org\/10.1016\/j.tig.2007.09.001 (2007).","journal-title":"Trends Genet."},{"key":"58452_CR7","doi-asserted-by":"publisher","first-page":"45","DOI":"10.25259\/JCIS_116_2019","volume":"9","author":"A Thomas","year":"2019","unstructured":"Thomas, A. & Thomas, A. K. POLR3-related Leukodystrophy. J. Clin. Imaging Sci. 9, 45. https:\/\/doi.org\/10.25259\/JCIS_116_2019 (2019).","journal-title":"J. Clin. Imaging Sci."},{"key":"58452_CR8","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1042\/BCJ20180239","volume":"475","author":"P Sosinska-Zawierucha","year":"2018","unstructured":"Sosinska-Zawierucha, P., Zawierucha, P., Breborowicz, A. & Barciszewski, J. Prediction of secondary and tertiary structures of human BC200 RNA (BCYRN1) based on experimental and bioinformatic cross-validation. Biochem. J. 475, 2727\u20132748. https:\/\/doi.org\/10.1042\/BCJ20180239 (2018).","journal-title":"Biochem. J."},{"key":"58452_CR9","doi-asserted-by":"publisher","first-page":"e202201496","DOI":"10.26508\/lsa.202201496","volume":"5","author":"IA Muslimov","year":"2022","unstructured":"Muslimov, I. A. et al. Autoimmune RNA dysregulation and seizures: Therapeutic prospects in neuropsychiatric lupus. Life Sci. Alliance 5, e202201496. https:\/\/doi.org\/10.26508\/lsa.202201496 (2022).","journal-title":"Life Sci. Alliance"},{"key":"58452_CR10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1101\/gr.176925.114","volume":"25","author":"G Borck","year":"2015","unstructured":"Borck, G. et al. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies. Genome Res. 25, 155\u2013166. https:\/\/doi.org\/10.1101\/gr.176925.114 (2015).","journal-title":"Genome Res."},{"key":"58452_CR11","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ajhg.2018.02.011","volume":"102","author":"MI Mendes","year":"2018","unstructured":"Mendes, M. I. et al. Bi-allelic mutations in EPRS, encoding the glutamyl-prolyl-aminoacyl-tRNA synthetase, cause a hypomyelinating leukodystrophy. Am. J. Hum. Genet. 102, 676\u2013684. https:\/\/doi.org\/10.1016\/j.ajhg.2018.02.011 (2018).","journal-title":"Am. J. Hum. Genet."},{"key":"58452_CR12","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1002\/humu.23250","volume":"38","author":"T Nakayama","year":"2017","unstructured":"Nakayama, T. et al. Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive syndrome of progressive microcephaly, hypomyelination, and epileptic encephalopathy. Hum. Mutat. 38, 1348\u20131354. https:\/\/doi.org\/10.1002\/humu.23250 (2017).","journal-title":"Hum. Mutat."},{"key":"58452_CR13","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.cell.2014.03.049","volume":"157","author":"AE Schaffer","year":"2014","unstructured":"Schaffer, A. E. et al. CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 157, 651\u2013663. https:\/\/doi.org\/10.1016\/j.cell.2014.03.049 (2014).","journal-title":"Cell"},{"key":"58452_CR14","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.3390\/biomedicines10092276","volume":"10","author":"A Musumeci","year":"2022","unstructured":"Musumeci, A. et al. Identification of a novel missense mutation of POLR3A gene in a cohort of sicilian patients with leukodystrophy. Biomedicines 10, 2276. https:\/\/doi.org\/10.3390\/biomedicines10092276 (2022).","journal-title":"Biomedicines"},{"key":"58452_CR15","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.ajhg.2011.07.014","volume":"89","author":"G Bernard","year":"2011","unstructured":"Bernard, G. et al. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am. J. Hum. Genet. 89, 415\u2013423. https:\/\/doi.org\/10.1016\/j.ajhg.2011.07.014 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"58452_CR16","doi-asserted-by":"publisher","first-page":"e521","DOI":"10.1212\/NXG.0000000000000521","volume":"6","author":"V Zanette","year":"2020","unstructured":"Zanette, V. et al. Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations. Neurol. Genet. 6, e521. https:\/\/doi.org\/10.1212\/NXG.0000000000000521 (2020).","journal-title":"Neurol. Genet."},{"key":"58452_CR17","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.tcb.2018.03.007","volume":"28","author":"V Tiku","year":"2018","unstructured":"Tiku, V. & Antebi, A. Nucleolar function in lifespan regulation. Trends Cell Biol. 28, 662\u2013672. https:\/\/doi.org\/10.1016\/j.tcb.2018.03.007 (2018).","journal-title":"Trends Cell Biol."},{"key":"58452_CR18","doi-asserted-by":"publisher","first-page":"111360","DOI":"10.1016\/j.mad.2020.111360","volume":"192","author":"CT Baez-Becerra","year":"2020","unstructured":"Baez-Becerra, C. T. et al. Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch syndrome fibroblasts. Mech. Ageing Dev. 192, 111360. https:\/\/doi.org\/10.1016\/j.mad.2020.111360 (2020).","journal-title":"Mech. Ageing Dev."},{"key":"58452_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13023-015-0279-9","volume":"10","author":"M Gutierrez","year":"2015","unstructured":"Gutierrez, M. et al. Large exonic deletions in POLR3B gene cause POLR3-related leukodystrophy. Orphanet J. Rare Dis. 10, 69. https:\/\/doi.org\/10.1186\/s13023-015-0279-9 (2015).","journal-title":"Orphanet J. Rare Dis."},{"key":"58452_CR20","doi-asserted-by":"publisher","first-page":"7445","DOI":"10.1074\/jbc.RA118.006271","volume":"294","author":"K Choquet","year":"2019","unstructured":"Choquet, K. et al. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. J. Biol. Chem. 294, 7445\u20137459. https:\/\/doi.org\/10.1074\/jbc.RA118.006271 (2019).","journal-title":"J. Biol. Chem."},{"key":"58452_CR21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13041-017-0294-y","volume":"10","author":"K Choquet","year":"2017","unstructured":"Choquet, K. et al. Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation. Mol. Brain 10, 13. https:\/\/doi.org\/10.1186\/s13041-017-0294-y (2017).","journal-title":"Mol. Brain"},{"key":"58452_CR22","doi-asserted-by":"publisher","first-page":"3687","DOI":"10.4161\/cc.9.18.13203","volume":"9","author":"H Dumay-Odelot","year":"2010","unstructured":"Dumay-Odelot, H., Durrieu-Gaillard, S., Da Silva, D., Roeder, R. G. & Teichmann, M. Cell growth- and differentiation-dependent regulation of RNA polymerase III transcription. Cell Cycle 9, 3687\u20133699. https:\/\/doi.org\/10.4161\/cc.9.18.13203 (2010).","journal-title":"Cell Cycle"},{"key":"58452_CR23","doi-asserted-by":"publisher","first-page":"696438","DOI":"10.3389\/fmolb.2021.696438","volume":"8","author":"E Lata","year":"2021","unstructured":"Lata, E. et al. RNA polymerase III subunit mutations in genetic diseases. Front. Mol. Biosci. 8, 696438. https:\/\/doi.org\/10.3389\/fmolb.2021.696438 (2021).","journal-title":"Front. Mol. Biosci."},{"key":"58452_CR24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.tins.2019.01.002","volume":"42","author":"B Elbaz","year":"2019","unstructured":"Elbaz, B. & Popko, B. Molecular control of oligodendrocyte development. Trends Neurosci. 42, 263\u2013277. https:\/\/doi.org\/10.1016\/j.tins.2019.01.002 (2019).","journal-title":"Trends Neurosci."},{"key":"58452_CR25","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1038\/s41467-020-16694-8","volume":"11","author":"S Huang","year":"2020","unstructured":"Huang, S. et al. Ribosome engineering reveals the importance of 5S rRNA autonomy for ribosome assembly. Nat. Commun. 11, 2900. https:\/\/doi.org\/10.1038\/s41467-020-16694-8 (2020).","journal-title":"Nat. Commun."},{"key":"58452_CR26","doi-asserted-by":"publisher","first-page":"e289","DOI":"10.1212\/NXG.0000000000000289","volume":"4","author":"I Dorboz","year":"2018","unstructured":"Dorboz, I. et al. Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation. Neurol. Genet. 4, e289. https:\/\/doi.org\/10.1212\/NXG.0000000000000289 (2018).","journal-title":"Neurol. Genet."},{"key":"58452_CR27","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/nar\/gkz1071","volume":"48","author":"K Roder","year":"2020","unstructured":"Roder, K., Stirnemann, G., Dock-Bregeon, A. C., Wales, D. J. & Pasquali, S. Structural transitions in the RNA 7SK 5\u2019 hairpin and their effect on HEXIM binding. Nucleic Acids Res. 48, 373\u2013389. https:\/\/doi.org\/10.1093\/nar\/gkz1071 (2020).","journal-title":"Nucleic Acids Res."},{"key":"58452_CR28","doi-asserted-by":"publisher","first-page":"e2100092","DOI":"10.1002\/bies.202100092","volume":"43","author":"M Briese","year":"2021","unstructured":"Briese, M. & Sendtner, M. Keeping the balance: The noncoding RNA 7SK as a master regulator for neuron development and function. Bioessays 43, e2100092. https:\/\/doi.org\/10.1002\/bies.202100092 (2021).","journal-title":"Bioessays"},{"key":"58452_CR29","doi-asserted-by":"publisher","first-page":"4302","DOI":"10.1093\/hmg\/ddw263","volume":"25","author":"DN Azmanov","year":"2016","unstructured":"Azmanov, D. N. et al. Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual phenotype of striatal involvement. Hum. Mol. Genet. 25, 4302\u20134314. https:\/\/doi.org\/10.1093\/hmg\/ddw263 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"58452_CR30","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1101\/gad.333989.119","volume":"34","author":"M Yeganeh","year":"2020","unstructured":"Yeganeh, M. & Hernandez, N. RNA polymerase III transcription as a disease factor. Genes Dev. 34, 865\u2013882. https:\/\/doi.org\/10.1101\/gad.333989.119 (2020).","journal-title":"Genes Dev."},{"key":"58452_CR31","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s12943-017-0679-7","volume":"16","author":"EP Booy","year":"2017","unstructured":"Booy, E. P., McRae, E. K., Koul, A., Lin, F. & McKenna, S. A. The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol. Cancer 16, 109. https:\/\/doi.org\/10.1186\/s12943-017-0679-7 (2017).","journal-title":"Mol. Cancer"},{"key":"58452_CR32","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/neu.480260212","volume":"26","author":"J McLaurin","year":"1995","unstructured":"McLaurin, J., Trudel, G. C., Shaw, I. T., Antel, J. P. & Cashman, N. R. A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype. J. Neurobiol. 26, 283\u2013293. https:\/\/doi.org\/10.1002\/neu.480260212 (1995).","journal-title":"J. Neurobiol."},{"key":"58452_CR33","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1007\/s00018-006-6094-7","volume":"63","author":"JM Boggs","year":"2006","unstructured":"Boggs, J. M. Myelin basic protein: A multifunctional protein. Cell. Mol. Life Sci. 63, 1945\u20131961. https:\/\/doi.org\/10.1007\/s00018-006-6094-7 (2006).","journal-title":"Cell. Mol. Life Sci."},{"key":"58452_CR34","doi-asserted-by":"publisher","first-page":"e1529","DOI":"10.1038\/cddis.2014.483","volume":"5","author":"V Voccoli","year":"2014","unstructured":"Voccoli, V., Tonazzini, I., Signore, G., Caleo, M. & Cecchini, M. Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death. Cell Death Dis. 5, e1529. https:\/\/doi.org\/10.1038\/cddis.2014.483 (2014).","journal-title":"Cell Death Dis."},{"key":"58452_CR35","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s12883-020-01835-9","volume":"20","author":"R Campopiano","year":"2020","unstructured":"Campopiano, R. et al. A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset. BMC Neurol. 20, 258. https:\/\/doi.org\/10.1186\/s12883-020-01835-9 (2020).","journal-title":"BMC Neurol."},{"key":"58452_CR36","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12887-018-1108-9","volume":"18","author":"VV Tewari","year":"2018","unstructured":"Tewari, V. V. et al. A novel homozygous mutation in POLR3A gene causing 4H syndrome: A case report. BMC Pediatr. 18, 126. https:\/\/doi.org\/10.1186\/s12887-018-1108-9 (2018).","journal-title":"BMC Pediatr."},{"key":"58452_CR37","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1212\/WNL.0000000000001002","volume":"83","author":"NI Wolf","year":"2014","unstructured":"Wolf, N. I. et al. Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations. Neurology 83, 1898\u20131905. https:\/\/doi.org\/10.1212\/WNL.0000000000001002 (2014).","journal-title":"Neurology"},{"key":"58452_CR38","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.1093\/brain\/awq257","volume":"133","author":"ME Steenweg","year":"2010","unstructured":"Steenweg, M. E. et al. Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain 133, 2971\u20132982. https:\/\/doi.org\/10.1093\/brain\/awq257 (2010).","journal-title":"Brain"},{"key":"58452_CR39","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1055\/s-0037-1599141","volume":"48","author":"S Vrij-van den Bos","year":"2017","unstructured":"Vrij-van den Bos, S. et al. 4H leukodystrophy: A brain magnetic resonance imaging scoring system. Neuropediatrics 48, 152\u2013160. https:\/\/doi.org\/10.1055\/s-0037-1599141 (2017).","journal-title":"Neuropediatrics"},{"key":"58452_CR40","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s12887-019-1656-7","volume":"19","author":"S Wu","year":"2019","unstructured":"Wu, S. et al. Novel mutations of the POLR3A gene caused POLR3-related leukodystrophy in a Chinese family: A case report. BMC Pediatr. 19, 289. https:\/\/doi.org\/10.1186\/s12887-019-1656-7 (2019).","journal-title":"BMC Pediatr."},{"key":"58452_CR41","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1212\/WNL.0000000000002612","volume":"86","author":"R La Piana","year":"2016","unstructured":"La Piana, R. et al. Diffuse hypomyelination is not obligate for POLR3-related disorders. Neurology 86, 1622\u20131626. https:\/\/doi.org\/10.1212\/WNL.0000000000002612 (2016).","journal-title":"Neurology"},{"key":"58452_CR42","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s10048-019-00602-4","volume":"21","author":"I Harting","year":"2020","unstructured":"Harting, I. et al. POLR3A variants with striatal involvement and extrapyramidal movement disorder. Neurogenetics 21, 121\u2013133. https:\/\/doi.org\/10.1007\/s10048-019-00602-4 (2020).","journal-title":"Neurogenetics"},{"key":"58452_CR43","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1177\/0883073813503902","volume":"29","author":"R La Piana","year":"2014","unstructured":"La Piana, R. et al. Brain magnetic resonance imaging (MRI) pattern recognition in Pol III-related leukodystrophies. J. Child Neurol. 29, 214\u2013220. https:\/\/doi.org\/10.1177\/0883073813503902 (2014).","journal-title":"J. Child Neurol."},{"key":"58452_CR44","doi-asserted-by":"publisher","first-page":"e29320","DOI":"10.7759\/cureus.29320","volume":"14","author":"MA Ghamry","year":"2022","unstructured":"Ghamry, M. A., Salah, R., Galal, E. I., Henin, S. & Dobs, M. A case of Wiedemann-Rautenstrauch syndrome with fatal hyperkalemic renal faliure. Cureus 14, e29320. https:\/\/doi.org\/10.7759\/cureus.29320 (2022).","journal-title":"Cureus"},{"key":"58452_CR45","doi-asserted-by":"publisher","first-page":"314594","DOI":"10.1155\/2015\/314594","volume":"2015","author":"E Billington","year":"2015","unstructured":"Billington, E., Bernard, G., Gibson, W. & Corenblum, B. Endocrine aspects of 4H leukodystrophy: A case report and review of the literature. Case Rep. Endocrinol. 2015, 314594. https:\/\/doi.org\/10.1155\/2015\/314594 (2015).","journal-title":"Case Rep. Endocrinol."}],"updated-by":[{"DOI":"10.1038\/s41598-024-72293-3","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-58452-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-58452-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-58452-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T14:09:16Z","timestamp":1725977356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-58452-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["58452"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-58452-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,1]]},"assertion":[{"value":"6 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-024-72293-3","URL":"https:\/\/doi.org\/10.1038\/s41598-024-72293-3","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7638"}}