{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:03:54Z","timestamp":1791230634286,"version":"4.1.0"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["IZSTZ0_216615"],"award-info":[{"award-number":["IZSTZ0_216615"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["IZSTZ0_216615"],"award-info":[{"award-number":["IZSTZ0_216615"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_182632"],"award-info":[{"award-number":["31003A_182632"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["IZSTZ0_216615"],"award-info":[{"award-number":["IZSTZ0_216615"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_182632"],"award-info":[{"award-number":["31003A_182632"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["18382019A"],"award-info":[{"award-number":["18382019A"]}],"id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["18382019A"],"award-info":[{"award-number":["18382019A"]}],"id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["18382019A"],"award-info":[{"award-number":["18382019A"]}],"id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["18382019A"],"award-info":[{"award-number":["18382019A"]}],"id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010221","name":"Higher Education Commision, Pakistan","doi-asserted-by":"publisher","award":["1-8\/HEC\/HRD\/2020\/10867"],"award-info":[{"award-number":["1-8\/HEC\/HRD\/2020\/10867"]}],"id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010221","name":"Higher Education Commision, Pakistan","doi-asserted-by":"publisher","award":["1-8\/HEC\/HRD\/2020\/10867"],"award-info":[{"award-number":["1-8\/HEC\/HRD\/2020\/10867"]}],"id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006390","name":"University of Lausanne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006390","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract\n<\/jats:title>\n          <jats:sec>\n            <jats:title>Background\n<\/jats:title>\n            <jats:p>Variants in genes encoding multiple subunits of the RNA Polymerase III complex which synthesizes rRNAs, tRNAs, and other small RNAs were previously associated with neurological disorders, such as syndromic hypomyelination leukodystrophies, pontocerebellar hypoplasia, and cerebellofaciodental syndrome. One new such candidate is <jats:italic>BRF2<\/jats:italic>, which encodes a TFIIB-like factor that recruits the RNA polymerase III complex to type 3 promoters to initiate transcription of U6, RnaseP, and 7SK RNAs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We combined sequencing with functional analyses to investigate the effects of <jats:italic>BRF2<\/jats:italic> variants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We observe that a previously reported significant underrepresentation of double transmission of a splice variant results in recessive lethality in three large Icelandic families with multiple perinatal losses. Using data aggregation, we identified an additional seven individuals worldwide from three unrelated families carrying biallelic variants in <jats:italic>BRF2<\/jats:italic>. Affected individuals present a variable phenotype ranging from severe craniofacial anomalies with early death to intellectual disability with motor and speech development. In silico 3D modelling and functional analyses showed functional impairment of the identified variants, e.g., differences in target loci occupancy. Zebrafish knocked down for the orthologous <jats:italic>brf2<\/jats:italic> presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. These defects were complemented by the human wild-type but not mutated BRF2 mRNA further demonstrating their deleteriousness.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Overall, our results support the association of biallelic <jats:italic>BRF2<\/jats:italic> variants with a novel neurodevelopmental disease and provide an additional link between RNA polymerase III, its targets and craniofacial anomalies.\n<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13073-025-01463-3","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T08:23:21Z","timestamp":1744619001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bi-allelic variants in BRF2 are associated with perinatal death and craniofacial anomalies"],"prefix":"10.1186","volume":"17","author":[{"given":"Francesca","family":"Mattioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fan","family":"Fri\u00f0riksd\u00f3ttir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sissy","family":"Bassani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shagufta","family":"Naz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Chrast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Pailler-Pradeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1smundur","family":"Oddsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Sulem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisli H.","family":"Halldorsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1ll","family":"Melsted","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u00edel F.","family":"Gu\u00f0bjartsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Palombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Pippucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayereh","family":"Nouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Seri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily G.","family":"Farrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol J.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Guex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Stefansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Reymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"issue":"10","key":"1463_CR1","first-page":"862","volume":"8","author":"RP Verma","year":"2021","unstructured":"Verma RP. Evaluation and risk assessment of congenital anomalies in neonates. Children (Basel). 2021;8(10):862.","journal-title":"Children (Basel)"},{"issue":"4","key":"1463_CR2","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1007\/s00431-023-04865-w","volume":"182","author":"L Kang","year":"2023","unstructured":"Kang L, Cao G, Jing W, Liu J, Liu M. Global, regional, and national incidence and mortality of congenital birth defects from 1990 to 2019. Eur J Pediatr. 2023;182(4):1781\u201392.","journal-title":"Eur J Pediatr"},{"issue":"1","key":"1463_CR3","doi-asserted-by":"publisher","first-page":"e067033","DOI":"10.1136\/bmjopen-2022-067033","volume":"13","author":"J Perin","year":"2023","unstructured":"Perin J, Mai CT, Costa AD, Strong K, Diaz T, Blencowe H, et al. Systematic estimates of the global, regional and national under-5 mortality burden attributable to birth defects in 2000\u20132019: a summary of findings from the 2020 WHO estimates. BMJ Open. 2023;13(1):e067033.","journal-title":"BMJ Open"},{"issue":"1","key":"1463_CR4","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00431-021-04213-w","volume":"181","author":"A Marouane","year":"2022","unstructured":"Marouane A, Olde Keizer RACM, Frederix GWJ, Vissers LELM, de Boode WP, van Zelst-Stams WAG. Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study. Eur J Pediatr. 2022;181(1):359\u201367.","journal-title":"Eur J Pediatr"},{"issue":"12","key":"1463_CR5","doi-asserted-by":"publisher","first-page":"e173438","DOI":"10.1001\/jamapediatrics.2017.3438","volume":"171","author":"L Meng","year":"2017","unstructured":"Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, et al. Use of exome sequencing for infants in intensive care units: ascertainment of severe single-gene disorders and effect on medical management. JAMA Pediatr. 2017;171(12):e173438.","journal-title":"JAMA Pediatr"},{"issue":"10173","key":"1463_CR6","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/S0140-6736(18)32042-7","volume":"393","author":"S Petrovski","year":"2019","unstructured":"Petrovski S, Aggarwal V, Giordano JL, Stosic M, Wou K, Bier L, et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. The Lancet. 2019;393(10173):758\u201367.","journal-title":"The Lancet"},{"issue":"10173","key":"1463_CR7","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/S0140-6736(18)31940-8","volume":"393","author":"J Lord","year":"2019","unstructured":"Lord J, McMullan DJ, Eberhardt RY, Rinck G, Hamilton SJ, Quinlan-Jones E, et al. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019;393(10173):747\u201357.","journal-title":"Lancet"},{"issue":"1","key":"1463_CR8","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1056\/NEJM198901053200104","volume":"320","author":"K Nelson","year":"1989","unstructured":"Nelson K, Holmes LB. Malformations due to presumed spontaneous mutations in newborn infants. N Engl J Med. 1989;320(1):19\u201323.","journal-title":"N Engl J Med"},{"issue":"5","key":"1463_CR9","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1086\/503875","volume":"78","author":"CG Woods","year":"2006","unstructured":"Woods CG, Cox J, Springell K, Hampshire DJ, Mohamed MD, McKibbin M, et al. Quantification of homozygosity in consanguineous individuals with autosomal recessive disease. Am J Hum Genet. 2006;78(5):889\u201396.","journal-title":"Am J Hum Genet"},{"issue":"12","key":"1463_CR10","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/gim.2016.37","volume":"18","author":"M Abouelhoda","year":"2016","unstructured":"Abouelhoda M, Sobahy T, El-Kalioby M, Patel N, Shamseldin H, Monies D, et al. Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden. Genet Med. 2016;18(12):1244\u20139.","journal-title":"Genet Med"},{"issue":"1\u20134","key":"1463_CR11","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1159\/000362598","volume":"77","author":"PC Corry","year":"2014","unstructured":"Corry PC. Consanguinity and prevalence patterns of inherited disease in the UK Pakistani Community. Hum Hered. 2014;77(1\u20134):207\u201316.","journal-title":"Hum Hered"},{"issue":"1","key":"1463_CR12","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/ajmg.10311","volume":"109","author":"J Zlotogora","year":"2002","unstructured":"Zlotogora J. What is the birth defect risk associated with consanguineous marriages? Am J Med Genet. 2002;109(1):70\u20131.","journal-title":"Am J Med Genet"},{"issue":"9901","key":"1463_CR13","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1016\/S0140-6736(13)61132-0","volume":"382","author":"E Sheridan","year":"2013","unstructured":"Sheridan E, Wright J, Small N, Corry PC, Oddie S, Whibley C, et al. Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study. Lancet. 2013;382(9901):1350\u20139.","journal-title":"Lancet"},{"issue":"3","key":"1463_CR14","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.ajhg.2019.07.011","volume":"105","author":"MJ Bamshad","year":"2019","unstructured":"Bamshad MJ, Nickerson DA, Chong JX. Mendelian gene discovery: fast and furious with no end in sight. Am J Human Genet. 2019;105(3):448\u201355.","journal-title":"Am J Human Genet"},{"issue":"11","key":"1463_CR15","doi-asserted-by":"publisher","first-page":"3266","DOI":"10.1002\/ajmg.a.62400","volume":"185","author":"SE Antonarakis","year":"2021","unstructured":"Antonarakis SE. History of the methodology of disease gene identification. Am J Med Genet A. 2021;185(11):3266\u201375.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"1463_CR16","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/ng.3243","volume":"47","author":"P Sulem","year":"2015","unstructured":"Sulem P, Helgason H, Oddson A, Stefansson H, Gudjonsson SA, Zink F, et al. Identification of a large set of rare complete human knockouts. Nat Genet. 2015;47(5):448\u201352.","journal-title":"Nat Genet"},{"issue":"1","key":"1463_CR17","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1038\/s41467-023-38951-2","volume":"14","author":"A Oddsson","year":"2023","unstructured":"Oddsson A, Sulem P, Sveinbjornsson G, Arnadottir GA, Steinthorsdottir V, Halldorsson GH, et al. Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality. Nat Commun. 2023;14(1):3453.","journal-title":"Nat Commun"},{"issue":"7649","key":"1463_CR18","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature22034","volume":"544","author":"D Saleheen","year":"2017","unstructured":"Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA, et al. Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature. 2017;544(7649):235\u20139.","journal-title":"Nature"},{"issue":"7809","key":"1463_CR19","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alf\u00f6ldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434\u201343.","journal-title":"Nature"},{"issue":"6284","key":"1463_CR20","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1126\/science.aac8624","volume":"352","author":"VM Narasimhan","year":"2016","unstructured":"Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Barnes MR, et al. Health and population effects of rare gene knockouts in adult humans with related parents. Science. 2016;352(6284):474\u20137.","journal-title":"Science"},{"issue":"20","key":"1463_CR21","doi-asserted-by":"publisher","first-page":"2650","DOI":"10.1101\/gad.836400","volume":"14","author":"L Schramm","year":"2000","unstructured":"Schramm L, Pendergrast PS, Sun Y, Hernandez N. Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters. Genes Dev. 2000;14(20):2650\u201363.","journal-title":"Genes Dev"},{"issue":"26","key":"1463_CR22","doi-asserted-by":"publisher","first-page":"14200","DOI":"10.1073\/pnas.97.26.14200","volume":"97","author":"M Teichmann","year":"2000","unstructured":"Teichmann M, Wang Z, Roeder RG. A stable complex of a novel transcription factor IIB- related factor, human TFIIIB50, and associated proteins mediate selective transcription by RNA polymerase III of genes with upstream promoter elements. Proc Natl Acad Sci. 2000;97(26):14200\u20135.","journal-title":"Proc Natl Acad Sci"},{"key":"1463_CR23","doi-asserted-by":"crossref","unstructured":"Saxena A, Ma B, Schramm L, Hernandez N. Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA Polymerase III transcription. Mol Cell Biol. 2005; Available from: https:\/\/journals.asm.org\/doi\/abs\/10.1128\/MCB.25.21.9406-9418.2005. Cited 2022 Jan 19.","DOI":"10.1128\/MCB.25.21.9406-9418.2005"},{"issue":"6","key":"1463_CR24","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.cell.2015.11.005","volume":"163","author":"J Gouge","year":"2015","unstructured":"Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, et al. Redox signaling by the RNA Polymerase III TFIIB-related factor Brf2. Cell. 2015;163(6):1375\u201387.","journal-title":"Cell"},{"issue":"20","key":"1463_CR25","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1101\/gad.1018902","volume":"16","author":"L Schramm","year":"2002","unstructured":"Schramm L, Hernandez N. Recruitment of RNA polymerase III to its target promoters. Genes Dev. 2002;16(20):2593\u2013620.","journal-title":"Genes Dev"},{"issue":"10","key":"1463_CR26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1476-4598-10-47","volume":"25","author":"S Cabarcas","year":"2011","unstructured":"Cabarcas S, Schramm L. RNA polymerase III transcription in cancer: the BRF2 connection. Mol Cancer. 2011;25(10):47.","journal-title":"Mol Cancer"},{"issue":"3","key":"1463_CR27","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, Chouery E, Putorti ML, T\u00e9treault M, Takanohashi A, Carosso G, et al. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Human Genet. 2011;89(3):415\u201323.","journal-title":"Am J Human Genet"},{"issue":"7","key":"1463_CR28","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1002\/ajmg.a.38246","volume":"173","author":"S Paolacci","year":"2017","unstructured":"Paolacci S, Bertola D, Franco J, Mohammed S, Tartaglia M, Wollnik B, et al. Wiedemann-Rautenstrauch syndrome: A phenotype analysis. Am J Med Genet A. 2017;173(7):1763\u201372.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"1463_CR29","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.ajhg.2011.10.003","volume":"89","author":"H Saitsu","year":"2011","unstructured":"Saitsu H, Osaka H, Sasaki M, Takanashi JI, Hamada K, Yamashita A, et al. Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am J Human Genet. 2011;89(5):644\u201351.","journal-title":"Am J Human Genet"},{"issue":"5","key":"1463_CR30","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.ajhg.2011.10.006","volume":"89","author":"M T\u00e9treault","year":"2011","unstructured":"T\u00e9treault M, Choquet K, Orcesi S, Tonduti D, Balottin U, Teichmann M, et al. Recessive Mutations in POLR3B, Encoding the Second Largest Subunit of Pol III, Cause a Rare Hypomyelinating Leukodystrophy. Am J Hum Genet. 2011;89(5):652\u20135.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"1463_CR31","doi-asserted-by":"publisher","first-page":"e289","DOI":"10.1212\/NXG.0000000000000289","volume":"4","author":"I Dorboz","year":"2018","unstructured":"Dorboz I, Dumay-Odelot H, Boussaid K, Bouyacoub Y, Barreau P, Samaan S, et al. Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation. Neurol Genet. 2018;4(6):e289.","journal-title":"Neurol Genet"},{"issue":"1","key":"1463_CR32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41431-019-0427-0","volume":"28","author":"PA Terhal","year":"2020","unstructured":"Terhal PA, Vlaar JM, Middelkamp S, Nievelstein RAJ, Nikkels PGJ, Ross J, et al. Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia. Eur J Hum Genet. 2020;28(1):31\u20139.","journal-title":"Eur J Hum Genet"},{"issue":"4","key":"1463_CR33","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/s41431-019-0539-6","volume":"28","author":"E Beauregard-Lacroix","year":"2020","unstructured":"Beauregard-Lacroix E, Salian S, Kim H, Ehresmann S, D\u2019Amours G, Gauthier J, et al. A variant of neonatal progeroid syndrome, or Wiedemann\u2013Rautenstrauch syndrome, is associated with a nonsense variant in POLR3GL. Eur J Hum Genet. 2020;28(4):461\u20138.","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"1463_CR34","doi-asserted-by":"publisher","first-page":"7623","DOI":"10.1038\/ncomms8623","volume":"7","author":"I Thiffault","year":"2015","unstructured":"Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, et al. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III. Nat Commun. 2015;7(6):7623.","journal-title":"Nat Commun"},{"issue":"1","key":"1463_CR35","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/ng.724","volume":"43","author":"JG Dauwerse","year":"2011","unstructured":"Dauwerse JG, Dixon J, Seland S, Ruivenkamp CAL, van Haeringen A, Hoefsloot LH, et al. Mutations in genes encoding subunits of RNA polymerases I and III cause treacher Collins syndrome. Nat Genet. 2011;43(1):20\u20132.","journal-title":"Nat Genet"},{"issue":"13\u201314","key":"1463_CR36","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. 2020;34(13\u201314):865\u201382.","journal-title":"Genes Dev"},{"issue":"2","key":"1463_CR37","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1101\/gr.176925.114","volume":"25","author":"G Borck","year":"2015","unstructured":"Borck G, H\u00f6g F, Dentici ML, Tan PL, Sowada N, Medeira A, et al. BRF1 mutations alter RNA polymerase III\u2013dependent transcription and cause neurodevelopmental anomalies. Genome Res. 2015;25(2):155\u201366.","journal-title":"Genome Res"},{"issue":"11","key":"1463_CR38","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.1002\/ajmg.a.61839","volume":"182","author":"I Valenzuela","year":"2020","unstructured":"Valenzuela I, Codina M, Fern\u00e1ndez-\u00c1lvarez P, Mur P, Valle L, Tizzano EF, et al. Expanding the phenotype of cerebellar-facial-dental syndrome: Two siblings with a novel variant in BRF1. Am J Med Genet A. 2020;182(11):2742\u20135.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"1463_CR39","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/cge.12887","volume":"91","author":"YH Jee","year":"2017","unstructured":"Jee YH, Sowada N, Markello TC, Rezvani I, Borck G, Baron J. BRF1 mutations in a family with growth failure, markedly delayed bone age, and central nervous system anomalies. Clin Genet. 2017;91(5):739\u201347.","journal-title":"Clin Genet"},{"issue":"5","key":"1463_CR40","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1002\/ajmg.a.62140","volume":"185","author":"RS Honjo","year":"2021","unstructured":"Honjo RS, Castro MAA, Ferraciolli SF, Soares Junior LAV, Pastorino AC, Bertola DR, et al. Cerebellofaciodental syndrome in an adult patient: Expanding the phenotypic and natural history characteristics. Am J Med Genet A. 2021;185(5):1561\u20138.","journal-title":"Am J Med Genet A"},{"issue":"19","key":"1463_CR41","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1097\/CM9.0000000000001901","volume":"135","author":"X Zhao","year":"2022","unstructured":"Zhao X, Lan Y, Miao J, Li G, Sun W, Qiu X, et al. A novel BRF1 mutation in two middle-aged siblings with cerebellofaciodental syndrome. Chin Med J (Engl). 2022;135(19):2375\u20137.","journal-title":"Chin Med J (Engl)"},{"issue":"14","key":"1463_CR42","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754\u201360.","journal-title":"Bioinformatics"},{"issue":"9","key":"1463_CR43","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297\u2013303.","journal-title":"Genome Res"},{"issue":"5","key":"1463_CR44","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/ng.3247","volume":"47","author":"DF Gudbjartsson","year":"2015","unstructured":"Gudbjartsson DF, Helgason H, Gudjonsson SA, Zink F, Oddson A, Gylfason A, et al. Large-scale whole-genome sequencing of the Icelandic population. Nat Genet. 2015;47(5):435\u201344.","journal-title":"Nat Genet"},{"issue":"11","key":"1463_CR45","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1007\/s00439-020-02187-7","volume":"139","author":"F Palombo","year":"2020","unstructured":"Palombo F, Graziano C, Al Wardy N, Nouri N, Marconi C, Magini P, et al. Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East. Hum Genet. 2020;139(11):1429\u201341.","journal-title":"Hum Genet"},{"issue":"20","key":"1463_CR46","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1093\/bioinformatics\/btu401","volume":"30","author":"A Magi","year":"2014","unstructured":"Magi A, Tattini L, Palombo F, Benelli M, Gialluisi A, Giusti B, et al. H3M2: detection of runs of homozygosity from whole-exome sequencing data. Bioinformatics. 2014;30(20):2852\u20139.","journal-title":"Bioinformatics"},{"issue":"6","key":"1463_CR47","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.gim.2022.02.007","volume":"24","author":"ASA Cohen","year":"2022","unstructured":"Cohen ASA, Farrow EG, Abdelmoity AT, Alaimo JT, Amudhavalli SM, Anderson JT, et al. Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes. Genet Med. 2022;24(6):1336\u201348.","journal-title":"Genet Med"},{"issue":"265","key":"1463_CR48","doi-asserted-by":"publisher","first-page":"265ra168","DOI":"10.1126\/scitranslmed.3010076","volume":"6","author":"SE Soden","year":"2014","unstructured":"Soden SE, Saunders CJ, Willig LK, Farrow EG, Smith LD, Petrikin JE, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med. 2014;6(265):265ra168.","journal-title":"Sci Transl Med"},{"issue":"4","key":"1463_CR49","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1002\/humu.22529","volume":"35","author":"AA Alfaiz","year":"2014","unstructured":"Alfaiz AA, Micale L, Mandriani B, Augello B, Pellico MT, Chrast J, et al. TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease. Hum Mutat. 2014;35(4):447\u201351.","journal-title":"Hum Mutat"},{"issue":"1","key":"1463_CR50","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41525-021-00255-z","volume":"6","author":"F Mattioli","year":"2021","unstructured":"Mattioli F, Darvish H, Paracha SA, Tafakhori A, Firouzabadi SG, Chapi M, et al. Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder. NPJ Genom Med. 2021;6(1):94.","journal-title":"NPJ Genom Med"},{"issue":"11","key":"1463_CR51","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/s41588-019-0528-2","volume":"51","author":"AR Martin","year":"2019","unstructured":"Martin AR, Williams E, Foulger RE, Leigh S, Daugherty LC, Niblock O, et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019;51(11):1560\u20135.","journal-title":"Nat Genet"},{"issue":"15","key":"1463_CR52","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1002\/elps.1150181505","volume":"18","author":"N Guex","year":"1997","unstructured":"Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997;18(15):2714\u201323.","journal-title":"Electrophoresis"},{"issue":"1","key":"1463_CR53","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/1471-2105-13-173","volume":"13","author":"MU Johansson","year":"2012","unstructured":"Johansson MU, Zoete V, Michielin O, Guex N. Defining and searching for structural motifs using DeepView\/Swiss-PdbViewer. BMC Bioinformatics. 2012;13(1):173.","journal-title":"BMC Bioinformatics"},{"issue":"15","key":"1463_CR54","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.jmb.2017.12.007","volume":"430","author":"L Zimmermann","year":"2018","unstructured":"Zimmermann L, Stephens A, Nam SZ, Rau D, K\u00fcbler J, Lozajic M, et al. A completely reimplemented MPI bioinformatics toolkit with a new HHpred Server at its Core. J Mol Biol. 2018;430(15):2237\u201343.","journal-title":"J Mol Biol"},{"issue":"7873","key":"1463_CR55","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583\u20139.","journal-title":"Nature"},{"issue":"D1","key":"1463_CR56","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","volume":"50","author":"M Varadi","year":"2022","unstructured":"Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, et al. AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 2022;50(D1):D439\u201344.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"1463_CR57","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1080\/15548627.2019.1569925","volume":"15","author":"A Agrotis","year":"2019","unstructured":"Agrotis A, Pengo N, Burden JJ, Ketteler R. Redundancy of human ATG4 protease isoforms in autophagy and LC3\/GABARAP processing revealed in cells. Autophagy. 2019;15(6):976\u201397.","journal-title":"Autophagy"},{"issue":"7","key":"1463_CR58","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676\u201382.","journal-title":"Nat Methods"},{"issue":"7646","key":"1463_CR59","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/nature21683","volume":"543","author":"M Imbeault","year":"2017","unstructured":"Imbeault M, Helleboid PY, Trono D. KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks. Nature. 2017;543(7646):550\u20134.","journal-title":"Nature"},{"issue":"1","key":"1463_CR60","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41588-017-0004-9","volume":"50","author":"YI Li","year":"2018","unstructured":"Li YI, Knowles DA, Humphrey J, Barbeira AN, Dickinson SP, Im HK, et al. Annotation-free quantification of RNA splicing using LeafCutter. Nat Genet. 2018;50(1):151\u20138.","journal-title":"Nat Genet"},{"key":"1463_CR61","unstructured":"Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, D.C.: National Academies Press; 2011. Available from: http:\/\/www.nap.edu\/catalog\/12910. Cited 2023 Aug 29."},{"issue":"15","key":"1463_CR62","doi-asserted-by":"publisher","first-page":"e115","DOI":"10.1093\/nar\/gks596","volume":"40","author":"A Untergasser","year":"2012","unstructured":"Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M, et al. Primer3\u2013new capabilities and interfaces. Nucleic Acids Res. 2012;40(15):e115.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"1463_CR63","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, et al. The human genome browser at UCSC. Genome Res. 2002;12(6):996\u20131006.","journal-title":"Genome Res"},{"issue":"W1","key":"1463_CR64","doi-asserted-by":"publisher","first-page":"W171","DOI":"10.1093\/nar\/gkz365","volume":"47","author":"K Labun","year":"2019","unstructured":"Labun K, Montague TG, Krause M, Torres Cleuren YN, Tjeldnes H, Valen E. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res. 2019;47(W1):W171\u20134.","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"1463_CR65","doi-asserted-by":"publisher","first-page":"D886","DOI":"10.1093\/nar\/gky1016","volume":"47","author":"P Rentzsch","year":"2019","unstructured":"Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47(D1):D886\u201394.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"1463_CR66","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","volume":"176","author":"K Jaganathan","year":"2019","unstructured":"Jaganathan K, Kyriazopoulou Panagiotopoulou S, McRae JF, Darbandi SF, Knowles D, Li YI, et al. Predicting splicing from primary sequence with deep learning. Cell. 2019;176(3):535-548.e24.","journal-title":"Cell"},{"issue":"2\u20133","key":"1463_CR67","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1089\/1066527041410418","volume":"11","author":"G Yeo","year":"2004","unstructured":"Yeo G, Burge CB. Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing Signals. J Comput Biol. 2004;11(2\u20133):377\u201394.","journal-title":"J Comput Biol"},{"issue":"10","key":"1463_CR68","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1002\/humu.22844","volume":"36","author":"N Sobreira","year":"2015","unstructured":"Sobreira N, Schiettecatte F, Valle D, Hamosh A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat. 2015;36(10):928\u201330.","journal-title":"Hum Mutat"},{"issue":"3","key":"1463_CR69","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/ejhg.2008.221","volume":"17","author":"PA Trainor","year":"2009","unstructured":"Trainor PA, Dixon J, Dixon MJ. Treacher Collins syndrome: etiology, pathogenesis and prevention. Eur J Hum Genet. 2009;17(3):275\u201383.","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"1463_CR70","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","volume":"46","author":"M Kircher","year":"2014","unstructured":"Kircher M, Witten DM, Jain P, O\u2019Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310\u20135.","journal-title":"Nat Genet"},{"key":"1463_CR71","unstructured":"Koenig Z, Yohannes MT, Nkambule LL, Goodrich JK, Kim HA, Zhao X, et al. A harmonized public resource of deeply sequenced diverse human genomes. bioRxiv; 2023. p. 2023.01.23.525248. Available from: https:\/\/www.biorxiv.org\/content\/10.1101\/2023.01.23.525248v3. Cited 2024 Feb 6."},{"key":"1463_CR72","doi-asserted-by":"crossref","unstructured":"Ziyatdinov A, Torres J, Alegre-D\u00edaz J, Backman J, Mbatchou J, Turner M, et al. Genotyping, sequencing and analysis of 140,000 adults from the Mexico City Prospective Study. bioRxiv; 2022. p. 2022.06.26.495014. Cited 2023 Aug 18. Available from: https:\/\/www.biorxiv.org\/content\/10.1101\/2022.06.26.495014v1.","DOI":"10.1101\/2022.06.26.495014"},{"issue":"11","key":"1463_CR73","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1002\/humu.23880","volume":"40","author":"Z Fattahi","year":"2019","unstructured":"Fattahi Z, Beheshtian M, Mohseni M, Poustchi H, Sellars E, Nezhadi SH, et al. Iranome: A catalog of genomic variations in the Iranian population. Hum Mutat. 2019;40(11):1968\u201384.","journal-title":"Hum Mutat"},{"issue":"10","key":"1463_CR74","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1097\/00007611-199810000-00015","volume":"91","author":"SG Golombek","year":"1998","unstructured":"Golombek SG, Clement LT, Begleiter M, Truog WE. Immunodeficiency in a patient with Baller-Gerold syndrome: a reason for early demise? South Med J. 1998;91(10):966\u20139.","journal-title":"South Med J"},{"issue":"5","key":"1463_CR75","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","volume":"11","author":"PC Ng","year":"2001","unstructured":"Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11(5):863\u201374.","journal-title":"Genome Res"},{"key":"1463_CR76","doi-asserted-by":"publisher","unstructured":"Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013. Chapter 7:Unit7.20 https:\/\/doi.org\/10.1002\/0471142905.hg0720s76.\u00a0","DOI":"10.1002\/0471142905.hg0720s76"},{"issue":"4","key":"1463_CR77","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","volume":"99","author":"NM Ioannidis","year":"2016","unstructured":"Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, et al. REVEL: an ensemble method for predicting the pathogenicity of rare missense variants. Am J Hum Genet. 2016;99(4):877\u201385.","journal-title":"Am J Hum Genet"},{"issue":"12","key":"1463_CR78","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","volume":"53","author":"E Ferkingstad","year":"2021","unstructured":"Ferkingstad E, Sulem P, Atlason BA, Sveinbjornsson G, Magnusson MI, Styrmisdottir EL, et al. Large-scale integration of the plasma proteome with genetics and disease. Nat Genet. 2021;53(12):1712\u201321.","journal-title":"Nat Genet"},{"issue":"11","key":"1463_CR79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003028","volume":"8","author":"N James Faresse","year":"2012","unstructured":"James Faresse N, Canella D, Praz V, Michaud J, Romascano D, Hernandez N. Genomic study of RNA polymerase II and III SNAPc-bound promoters reveals a gene transcribed by both enzymes and a broad use of common activators. PLoS Genet. 2012;8(11): e1003028.","journal-title":"PLoS Genet"},{"key":"1463_CR80","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1146\/annurev.genet.40.110405.090439","volume":"41","author":"K Dolinski","year":"2007","unstructured":"Dolinski K, Botstein D. Orthology and functional conservation in eukaryotes. Annu Rev Genet. 2007;41:465\u2013507.","journal-title":"Annu Rev Genet"},{"issue":"9","key":"1463_CR81","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/gim.2014.12","volume":"16","author":"E Schaefer","year":"2014","unstructured":"Schaefer E, Collet C, Genevieve D, Vincent M, Lohmann DR, Sanchez E, et al. Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genet Med. 2014;16(9):720\u20134.","journal-title":"Genet Med"},{"key":"1463_CR82","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.696438","volume":"8","author":"E Lata","year":"2021","unstructured":"Lata E, Choquet K, Sagliocco F, Brais B, Bernard G, Teichmann M. RNA Polymerase III Subunit Mutations in Genetic Diseases. Front Mol Biosci. 2021;8: 696438.","journal-title":"Front Mol Biosci"},{"issue":"19","key":"1463_CR83","doi-asserted-by":"publisher","first-page":"4302","DOI":"10.1093\/hmg\/ddw263","volume":"25","author":"DN Azmanov","year":"2016","unstructured":"Azmanov DN, Siira SJ, Chamova T, Kaprelyan A, Guergueltcheva V, Shearwood AMJ, et al. Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual phenotype of striatal involvement. Hum Mol Genet. 2016;25(19):4302\u201314.","journal-title":"Hum Mol Genet"},{"issue":"18","key":"1463_CR84","doi-asserted-by":"publisher","first-page":"7445","DOI":"10.1074\/jbc.RA118.006271","volume":"294","author":"K Choquet","year":"2019","unstructured":"Choquet K, Forget D, Meloche E, Dicaire MJ, Bernard G, Vanderver A, et al. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. J Biol Chem. 2019;294(18):7445\u201359.","journal-title":"J Biol Chem"},{"issue":"2","key":"1463_CR85","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41594-020-00555-5","volume":"28","author":"M Girbig","year":"2021","unstructured":"Girbig M, Misiaszek AD, Vorl\u00e4nder MK, Lafita A, Gr\u00f6tsch H, Baudin F, et al. Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states. Nat Struct Mol Biol. 2021;28(2):210\u20139.","journal-title":"Nat Struct Mol Biol"},{"issue":"7","key":"1463_CR86","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41422-021-00472-2","volume":"31","author":"L Li","year":"2021","unstructured":"Li L, Yu Z, Zhao D, Ren Y, Hou H, Xu Y. Structure of human RNA polymerase III elongation complex. Cell Res. 2021;31(7):791\u2013800.","journal-title":"Cell Res"},{"issue":"7831","key":"1463_CR87","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41586-020-2832-5","volume":"586","author":"J Kaplanis","year":"2020","unstructured":"Kaplanis J, Samocha KE, Wiel L, Zhang Z, Arvai KJ, Eberhardt RY, et al. Evidence for 28 genetic disorders discovered by combining healthcare and research data. Nature. 2020;586(7831):757\u201362.","journal-title":"Nature"},{"issue":"6264","key":"1463_CR88","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1126\/science.aac7557","volume":"350","author":"VA Blomen","year":"2015","unstructured":"Blomen VA, M\u00e1jek P, Jae LT, Bigenzahn JW, Nieuwenhuis J, Staring J, et al. Gene essentiality and synthetic lethality in haploid human cells. Science. 2015;350(6264):1092\u20136.","journal-title":"Science"},{"issue":"6","key":"1463_CR89","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.cell.2015.11.015","volume":"163","author":"T Hart","year":"2015","unstructured":"Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, et al. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell. 2015;163(6):1515\u201326.","journal-title":"Cell"},{"issue":"6264","key":"1463_CR90","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1126\/science.aac7041","volume":"350","author":"T Wang","year":"2015","unstructured":"Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ, et al. Identification and characterization of essential genes in the human genome. Science. 2015;350(6264):1096\u2013101.","journal-title":"Science"},{"issue":"3","key":"1463_CR91","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.3892\/mmr.2020.11285","volume":"22","author":"Y Bian","year":"2020","unstructured":"Bian Y, Li Q, Li Q, Pan R. Silencing of BRF2 inhibits the growth and metastasis of lung cancer cells. Mol Med Rep. 2020;22(3):1767\u201374.","journal-title":"Mol Med Rep"},{"issue":"5","key":"1463_CR92","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nsmb.1801","volume":"17","author":"AJ Oler","year":"2010","unstructured":"Oler AJ, Alla RK, Roberts DN, Wong A, Hollenhorst PC, Chandler KJ, et al. Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat Struct Mol Biol. 2010;17(5):620\u20138.","journal-title":"Nat Struct Mol Biol"},{"key":"1463_CR93","doi-asserted-by":"crossref","unstructured":"Carri\u00e8re L, Graziani S, Alibert O, Ghavi-Helm Y, Boussouar F, Humbertclaude H, et al. Genomic binding of Pol III transcription machinery and relationship with TFIIS transcription factor distribution in mouse embryonic stem cells. Nucleic Acids Res. 2012;40(1):270\u201383.","DOI":"10.1093\/nar\/gkr737"},{"issue":"11","key":"1463_CR94","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1093\/emboj\/20.11.2823","volume":"20","author":"GA Kassavetis","year":"2001","unstructured":"Kassavetis GA, Letts GA, Geiduschek EP. The RNA polymerase III transcription initiation factor TFIIIB participates in two steps of promoter opening. EMBO J. 2001;20(11):2823\u201334.","journal-title":"EMBO J"},{"issue":"6","key":"1463_CR95","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/0092-8674(92)90399-W","volume":"71","author":"GA Kassavetis","year":"1992","unstructured":"Kassavetis GA, Joazeiro CA, Pisano M, Geiduschek EP, Colbert T, Hahn S, et al. The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor. TFIIIB Cell. 1992;71(6):1055\u201364.","journal-title":"TFIIIB Cell"},{"issue":"20","key":"1463_CR96","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","volume":"310","author":"World Medical Association","year":"2013","unstructured":"World Medical Association. World medical association declaration of helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191\u20134.","journal-title":"JAMA"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-025-01463-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-025-01463-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-025-01463-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:03:26Z","timestamp":1744621406000},"score":1,"resource":{"primary":{"URL":"https:\/\/genomemedicine.biomedcentral.com\/articles\/10.1186\/s13073-025-01463-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":96,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1463"],"URL":"https:\/\/doi.org\/10.1186\/s13073-025-01463-3","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]},"assertion":[{"value":"1 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from guardians of all participants in this study. The current study was approved by the respective IRBs, specifically the CER (Commission d\u2019\u00e9thique de la recherche) of the canton of Vaud (Protocol number: CER-VD 2021\u201301400), the Lahore College for Women University, the Children\u2019s Mercy Institutional Review Board (study #11120514), and the Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.MED.REC #189087). This research complies with the principles of the Declaration of Helsinki [].","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RF, AO, PS, GHH, PM, DFG, KS are employees of deCODE genetics\/Amgen Inc. The other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}