{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPOLR3A encodes the largest subunit of RNA polymerase III, a DNA‐dependent enzyme essential for the synthesis of a wide array of small noncoding RNAs – including all nuclear‐encoded transfer RNAs (tRNAs), 5S ribosomal RNA, and additional regulatory RNAs. Its normal function underpins critical cellular processes such as protein translation, RNA processing, and overall metabolic homeostasis. Defects or reduced expression of POLR3A disrupt the proper transcription of these RNAs, which can in turn perturb cytoplasmic protein synthesis and alter the balance of downstream gene expression programs.<br />."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in transcription, POLR3A also contributes to cellular defense and genomic maintenance. RNA polymerase III acts in innate immunity by functioning as a cytosolic DNA sensor that synthesizes RNA intermediates which subsequently trigger RIG-I–dependent interferon responses against viral pathogens such as varicella zoster virus. In addition, it participates in DNA double‐strand break repair; newly synthesized RNA can hybridize to the resected 3′ single-stranded DNA overhangs and thereby protect them during homologous recombination repair.<br />."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in POLR3A give rise to a diverse spectrum of human disorders that include hypomyelinating leukodystrophies, spastic ataxias, and neonatal progeroid syndromes such as Wiedemann–Rautenstrauch syndrome. Altered POLR3A function, whether through missense, splice‐altering, deep intronic, or truncating variants, leads to deregulated production of Pol III transcripts – notably tRNAs and regulatory noncoding RNAs – with downstream impacts on myelination, neurodevelopment, and even endocrine function. The clinical manifestations are heterogeneous, ranging from the classic hypomyelination accompanied by hypodontia and hypogonadotropic hypogonadism, to atypical presentations with predominant extrapyramidal features or progeroid appearances, as revealed by extensive genotype–phenotype correlations and unusual neuroimaging findings. Collectively, these studies emphasize that the integrity of POLR3A function is pivotal not only for maintaining basic cellular biosynthetic capacity but also for safeguarding genomic stability and mediating antiviral immunity.<br />."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Geneviève Bernard, Eliane Chouery, Maria Lisa Putorti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.07.014"}], "href": "https://doi.org/10.1016/j.ajhg.2011.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21855841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21855841"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hirotomo Saitsu, Hitoshi Osaka, Masayuki Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.10.003"}], "href": "https://doi.org/10.1016/j.ajhg.2011.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22036171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22036171"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomasz W Turowski, David Tollervey "}, {"type": "b", "children": [{"type": "t", "text": "Transcription by RNA polymerase III: insights into mechanism and regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20160062"}], "href": "https://doi.org/10.1042/BST20160062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27911719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27911719"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Aneeshkumar G Arimbasseri, Richard J Maraia "}, {"type": "b", "children": [{"type": "t", "text": "RNA Polymerase III Advances: Structural and tRNA Functional Views."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Biochem Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tibs.2016.03.003"}], "href": "https://doi.org/10.1016/j.tibs.2016.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27068803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27068803"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dimitar N Azmanov, Stefan J Siira, Teodora Chamova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual phenotype of striatal involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw263"}], "href": "https://doi.org/10.1093/hmg/ddw263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27506977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27506977"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jennifer A Wambach, Daniel J Wegner, Nivedita Patni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.10.010"}], "href": "https://doi.org/10.1016/j.ajhg.2018.10.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30414627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30414627"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Karine Choquet, Diane Forget, Elisabeth Meloche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukodystrophy-associated "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "POLR3A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutations down-regulate the RNA polymerase III transcript and important regulatory RNA "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "BC200"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.006271"}], "href": "https://doi.org/10.1074/jbc.RA118.006271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30898877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30898877"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Matthias K Vorländer, Florence Baudin, Robyn D Moir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for RNA polymerase III transcription repression by Maf1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41594-020-0383-y"}], "href": "https://doi.org/10.1038/s41594-020-0383-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32066962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32066962"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Karine Choquet, Sharon Yang, Robyn D Moir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Brain (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13041-017-0294-y"}], "href": "https://doi.org/10.1186/s13041-017-0294-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28407788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28407788"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Benson Ogunjimi, Shen-Ying Zhang, Katrine B Sørensen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI92280"}], "href": "https://doi.org/10.1172/JCI92280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28783042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28783042"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sijie Liu, Yu Hua, Jingna Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2021.01.048"}], "href": "https://doi.org/10.1016/j.cell.2021.01.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33626331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33626331"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Madalina E Carter-Timofte, Anders F Hansen, Mette Christiansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41435-018-0027-y"}], "href": "https://doi.org/10.1038/s41435-018-0027-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29728610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29728610"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yugen Zhang, Dirk P Dittmer, Piotr A Mieczkowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIG-I Detects Kaposi's Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "mBio (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/mBio.00823-18"}], "href": "https://doi.org/10.1128/mBio.00823-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29970461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29970461"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Madalina E Carter-Timofte, Søren R Paludan, Trine H Mogensen "}, {"type": "b", "children": [{"type": "t", "text": "RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmed.2018.07.009"}], "href": "https://doi.org/10.1016/j.molmed.2018.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30115567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30115567"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Nicole I Wolf, Adeline Vanderver, Rosalina M L van Spaendonk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000001002"}], "href": "https://doi.org/10.1212/WNL.0000000000001002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25339210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25339210"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Mandana Nikpour, Pravin Hissaria, Jillian Byron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Res Ther (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/ar3544"}], "href": "https://doi.org/10.1186/ar3544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22189167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22189167"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Hussein Daoud, Martine Tétreault, William Gibson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2012-101357"}], "href": "https://doi.org/10.1136/jmedgenet-2012-101357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23355746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23355746"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Martina Minnerop, Delia Kurzwelly, Holger Wagner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awx095"}], "href": "https://doi.org/10.1093/brain/awx095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28459997"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28459997"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Roberta La Piana, Ferdy K Cayami, Luan T Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diffuse hypomyelination is not obligate for POLR3-related disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000002612"}], "href": "https://doi.org/10.1212/WNL.0000000000002612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27029625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27029625"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Stefano Paolacci, Yun Li, Emanuele Agolini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific combinations of biallelic "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "POLR3A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " variants cause Wiedemann-Rautenstrauch syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2018-105528"}], "href": "https://doi.org/10.1136/jmedgenet-2018-105528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30323018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30323018"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Allison M Jay, Robert L Conway, Isabelle Thiffault, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neonatal progeriod syndrome associated with biallelic truncating variants in POLR3A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.37960"}], "href": "https://doi.org/10.1002/ajmg.a.37960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27612211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27612211"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Inga Harting, Murtadha Al-Saady, Ingeborg Krägeloh-Mann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POLR3A variants with striatal involvement and extrapyramidal movement disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-019-00602-4"}], "href": "https://doi.org/10.1007/s10048-019-00602-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31940116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31940116"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Johanna L Schmidt, Amy Pizzino, Jessica Nicholl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61641"}], "href": "https://doi.org/10.1002/ajmg.a.61641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32573057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32573057"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Félixe Pelletier, Stefanie Perrier, Ferdy K Cayami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/clinem/dgaa700"}], "href": "https://doi.org/10.1210/clinem/dgaa700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33005949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33005949"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jun-ichi Takanashi, Hitoshi Osaka, Hirotomo Saitsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.braindev.2013.03.006"}], "href": "https://doi.org/10.1016/j.braindev.2013.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23643445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23643445"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Davor Lessel, Ayse Bilge Ozel, Susan E Campbell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-018-1957-1"}], "href": "https://doi.org/10.1007/s00439-018-1957-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30450527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30450527"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Shuiyan Wu, Zhenjiang Bai, Xingqiang Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations of the POLR3A gene caused POLR3-related leukodystrophy in a Chinese family: a case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Pediatr (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12887-019-1656-7"}], "href": "https://doi.org/10.1186/s12887-019-1656-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31438894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31438894"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ferdy K Cayami, Roberta La Piana, Rosalina M L van Spaendonk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POLR3A and POLR3B Mutations in Unclassified Hypomyelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropediatrics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0035-1550148"}], "href": "https://doi.org/10.1055/s-0035-1550148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26011300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26011300"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Jon Infante, Karla M Serrano-Cárdenas, Marc Corral-Juan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POLR3A-related spastic ataxia: new mutations and a look into the phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00415-019-09574-9"}], "href": "https://doi.org/10.1007/s00415-019-09574-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31637490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31637490"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Takuya Hiraide, Mitsuko Nakashima, Takahiro Ikeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a deep intronic POLR3A variant causing inclusion of a pseudoexon derived from an Alu element in Pol III-related leukodystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-020-0786-y"}], "href": "https://doi.org/10.1038/s10038-020-0786-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32483275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32483275"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Stefanie Perrier, Laurence Gauquelin, Jennifer A Wambach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinguishing severe phenotypes associated with pathogenic variants in POLR3A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62553"}], "href": "https://doi.org/10.1002/ajmg.a.62553"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34773388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34773388"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Ilaria Di Donato, Antonio Gallo, Ivana Ricca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10072-021-05462-1"}], "href": "https://doi.org/10.1007/s10072-021-05462-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34296356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34296356"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Rosa Campopiano, Rosangela Ferese, Stefania Zampatti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Neurol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12883-020-01835-9"}], "href": "https://doi.org/10.1186/s12883-020-01835-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32600288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32600288"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Robyn D Moir, Christian Lavados, JaeHoon Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2020.145259"}], "href": "https://doi.org/10.1016/j.gene.2020.145259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33148458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33148458"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Amjad Khan, Bushra Al Shamsi, Maryam Al Shehhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Further delineation of Wiedemann-Rautenstrauch syndrome linked with POLR3A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.2274"}], "href": "https://doi.org/10.1002/mgg3.2274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38348603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38348603"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Dan-Dan Ruan, Xing-Lin Ruan, Ruo-Li Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-58452-6"}], "href": "https://doi.org/10.1038/s41598-024-58452-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38561452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38561452"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Ichraf Kraoua, Maha Jamoussi, Cyrine Drissi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.70007"}], "href": "https://doi.org/10.1002/mgg3.70007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39436788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39436788"}]}]}]}