{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:38:30Z","timestamp":1787499510703,"version":"build-2736575974"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1240\/16-1"],"award-info":[{"award-number":["KU 1240\/16-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum. Genet."],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s00439-025-02813-2","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:31:26Z","timestamp":1772191886000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A homozygous synonymous variant in SMG5, encoding a nonsense-mediated mRNA decay factor, causes developmental delay with growth retardation and relative macrocephaly"],"prefix":"10.1007","volume":"145","author":[{"given":"Debora","family":"Tibbe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tess","family":"Holling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Alawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Nampoothiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"2813_CR1","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/ajmg.a.62561","volume":"188","author":"GMH Abdel-Salam","year":"2022","unstructured":"Abdel-Salam GMH, Duan R, Abdel-Hamid MS, Sayed ISM, Jhangiani SN, Khan Z, Du H, Gibbs RA, Posey JE, Marafi D, Lupski JR (2022) Expanding the phenotypic and allelic spectrum of SMG8: clinical observations reveal overlap with SMG9-associated disease trait. Am J Med Genet A 188:648\u2013657. https:\/\/doi.org\/10.1002\/ajmg.a.62561","journal-title":"Am J Med Genet A"},{"key":"2813_CR2","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1002\/ajmg.a.62139","volume":"185","author":"N Altuwaijri","year":"2021","unstructured":"Altuwaijri N, Abdelbaky M, Alhashem A, Alrakaf M, Hashem M, Alzahrani F, Alkuraya FS (2021) Further delineation of SMG9-related heart and brain malformation syndrome. Am J Med Genet A 185:1624\u20131630. https:\/\/doi.org\/10.1002\/ajmg.a.62139","journal-title":"Am J Med Genet A"},{"key":"2813_CR3","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1016\/j.ajhg.2020.11.007","volume":"107","author":"F Alzahrani","year":"2020","unstructured":"Alzahrani F, Kuwahara H, Long Y, Al-Owain M, Tohary M, AlSayed M, Mahnashi M, Fathi L, Alnemer M, Al-Hamed MH, Lemire G, Boycott KM, Hashem M, Han W, Al-Maawali A, Al Mahrizi F, Al-Thihli K, Gao X, Alkuraya FS (2020) Recessive, deleterious variants in SMG8 expand the role of nonsense-mediated decay in developmental disorders in humans. Am J Hum Genet 107:1178\u20131185. https:\/\/doi.org\/10.1016\/j.ajhg.2020.11.007","journal-title":"Am J Hum Genet"},{"key":"2813_CR4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25:25\u201329. https:\/\/doi.org\/10.1038\/75556","journal-title":"Nat Genet"},{"key":"2813_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2025.102346","volume":"92","author":"S Bakshi","year":"2025","unstructured":"Bakshi S, Isom LL (2025) No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders. Curr Opin Genet Dev 92:102346. https:\/\/doi.org\/10.1016\/j.gde.2025.102346","journal-title":"Curr Opin Genet Dev"},{"key":"2813_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24046-3","volume":"12","author":"V Boehm","year":"2021","unstructured":"Boehm V, Kueckelmann S, Gerbracht JV, Kallabis S, Britto-Borges T, Altmuller J, Kruger M, Dieterich C, Gehring NH (2021) SMG5-SMG7 authorize nonsense-mediated mRNA decay by enabling SMG6 endonucleolytic activity. Nat Commun 12:3965. https:\/\/doi.org\/10.1038\/s41467-021-24046-3","journal-title":"Nat Commun"},{"key":"2813_CR7","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1002\/stem.1897","volume":"33","author":"O Candini","year":"2015","unstructured":"Candini O, Spano C, Murgia A, Grisendi G, Veronesi E, Piccinno MS, Ferracin M, Negrini M, Giacobbi F, Bambi F, Horwitz EM, Conte P, Paolucci P, Dominici M (2015) Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis. Stem Cells 33:939\u2013950. https:\/\/doi.org\/10.1002\/stem.1897","journal-title":"Stem Cells"},{"key":"2813_CR8","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen S, Zhou Y, Chen Y, Gu J (2018) Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34:i884\u2013i890. https:\/\/doi.org\/10.1093\/bioinformatics\/bty560","journal-title":"Bioinformatics"},{"key":"2813_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/biom14081023","author":"C Chen","year":"2024","unstructured":"Chen C, Wei Y, Jiang X, Li T (2024a) RNA surveillance factor SMG5 is essential for mouse embryonic stem cell differentiation. Biomolecules. https:\/\/doi.org\/10.3390\/biom14081023","journal-title":"Biomolecules"},{"key":"2813_CR10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","volume":"625","author":"S Chen","year":"2024","unstructured":"Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, Alfoldi J, Watts NA, Vittal C, Gauthier LD, Poterba T, Wilson MW, Tarasova Y, Phu W, Grant R, Yohannes MT, Koenig Z, Farjoun Y, Banks E, Donnelly S, Gabriel S, Gupta N, Ferriera S, Tolonen C, Novod S, Bergelson L, Roazen D, Ruano-Rubio V, Covarrubias M, Llanwarne C, Petrillo N, Wade G, Jeandet T, Munshi R, Tibbetts K, Genome Aggregation Database C, O\u2019Donnell-Luria A, Solomonson M, Seed C, Martin AR, Talkowski ME, Rehm HL, Daly MJ, Tiao G, Neale BM, MacArthur DG, Karczewski KJ (2024) A genomic mutational constraint map using variation in 76,156 human genomes. Nature 625:92\u2013100. https:\/\/doi.org\/10.1038\/s41586-023-06045-0","journal-title":"Nature"},{"key":"2813_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492","volume":"381","author":"J Cheng","year":"2023","unstructured":"Cheng J, Novati G, Pan J, Bycroft C, Zemgulyte A, Applebaum T, Pritzel A, Wong LH, Zielinski M, Sargeant T, Schneider RG, Senior AW, Jumper J, Hassabis D, Kohli P, Avsec Z (2023) Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science 381:eadg7492. https:\/\/doi.org\/10.1126\/science.adg7492","journal-title":"Science"},{"key":"2813_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1261\/rna.059055.116","volume":"23","author":"M Colombo","year":"2017","unstructured":"Colombo M, Karousis ED, Bourquin J, Bruggmann R, Muhlemann O (2017) Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive redundancy between SMG6- and SMG7-mediated degradation pathways. RNA 23:189\u2013201. https:\/\/doi.org\/10.1261\/rna.059055.116","journal-title":"RNA"},{"key":"2813_CR13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635","journal-title":"Bioinformatics"},{"key":"2813_CR14","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1038\/s41588-024-01872-x","volume":"56","author":"B Fair","year":"2024","unstructured":"Fair B, Buen Abad Najar CF, Zhao J, Lozano S, Reilly A, Mossian G, Staley JP, Wang J, Li YI (2024) Global impact of unproductive splicing on human gene expression. Nat Genet 56:1851\u20131861. https:\/\/doi.org\/10.1038\/s41588-024-01872-x","journal-title":"Nat Genet"},{"key":"2813_CR15","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1002\/ajmg.a.63242","volume":"191","author":"AA Fernandes","year":"2023","unstructured":"Fernandes AA, Grangeia A, Dias L, Guimaraes J (2023) Expanding the genetic spectrum of ALKU syndrome: compound heterozygosity for two deleterious variants in SMG8 gene. Am J Med Genet A 191:2204\u20132208. https:\/\/doi.org\/10.1002\/ajmg.a.63242","journal-title":"Am J Med Genet A"},{"key":"2813_CR16","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nrg3778","volume":"15","author":"XD Fu","year":"2014","unstructured":"Fu XD, Ares M Jr. (2014) Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet 15:689\u2013701. https:\/\/doi.org\/10.1038\/nrg3778","journal-title":"Nat Rev Genet"},{"key":"2813_CR17","first-page":"10459","volume":"8","author":"RT Gao","year":"2015","unstructured":"Gao RT, Zhan LP, Meng C, Zhang N, Chang SM, Yao R, Li C (2015) Homeobox B7 promotes the osteogenic differentiation potential of mesenchymal stem cells by activating RUNX2 and transcript of BSP. Int J Clin Exp Med 8:10459\u201310470","journal-title":"Int J Clin Exp Med"},{"key":"2813_CR18","doi-asserted-by":"publisher","first-page":"8626","DOI":"10.1093\/nar\/gkaa564","volume":"48","author":"JV Gerbracht","year":"2020","unstructured":"Gerbracht JV, Boehm V, Britto-Borges T, Kallabis S, Wiederstein JL, Ciriello S, Aschemeier DU, Kruger M, Frese CK, Altmuller J, Dieterich C, Gehring NH (2020) CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex. Nucleic Acids Res 48:8626\u20138644. https:\/\/doi.org\/10.1093\/nar\/gkaa564","journal-title":"Nucleic Acids Res"},{"key":"2813_CR19","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/nar\/gkx1272","volume":"46","author":"X Han","year":"2018","unstructured":"Han X, Wei Y, Wang H, Wang F, Ju Z, Li T (2018) Nonsense-mediated mRNA decay: a \u2018nonsense\u2019 pathway makes sense in stem cell biology. Nucleic Acids Res 46:1038\u20131051. https:\/\/doi.org\/10.1093\/nar\/gkx1272","journal-title":"Nucleic Acids Res"},{"key":"2813_CR20","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1101\/gad.347690.120","volume":"36","author":"M Huth","year":"2022","unstructured":"Huth M, Santini L, Galimberti E, Ramesmayer J, Titz-Teixeira F, Sehlke R, Oberhuemer M, Stummer S, Herzog V, Garmhausen M, Romeike M, Chugunova A, Leesch F, Holcik L, Weipoltshammer K, Lackner A, Schoefer C, von Haeseler A, Buecker C, Pauli A, Ameres SL, Smith A, Beyer A, Leeb M (2022) NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation. Genes Dev 36:348\u2013367. https:\/\/doi.org\/10.1101\/gad.347690.120","journal-title":"Genes Dev"},{"key":"2813_CR21","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, Musolf A, Li Q, Holzinger E, Karyadi D, Cannon-Albright LA, Teerlink CC, Stanford JL, Isaacs WB, Xu J, Cooney KA, Lange EM, Schleutker J, Carpten JD, Powell IJ, Cussenot O, Cancel-Tassin G, Giles GG, MacInnis RJ, Maier C, Hsieh CL, Wiklund F, Catalona WJ, Foulkes WD, Mandal D, Eeles RA, Kote-Jarai Z, Bustamante CD, Schaid DJ, Hastie T, Ostrander EA, Bailey-Wilson JE, Radivojac P, Thibodeau SN, Whittemore AS, Sieh W (2016) REVEL: an ensemble method for predicting the pathogenicity of rare missense variants. Am J Hum Genet 99:877\u2013885. https:\/\/doi.org\/10.1016\/j.ajhg.2016.08.016","journal-title":"Am J Hum Genet"},{"key":"2813_CR22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0371-25.2025","author":"M Jiang","year":"2025","unstructured":"Jiang M, Li C, Xie B, Li T, Dai ZM, Qiu M (2025) Smg5 enhances oligodendrocyte differentiation via nonsense-mediated mRNA decay of Hnrnpl variant transcripts. J Neurosci. https:\/\/doi.org\/10.1523\/JNEUROSCI.0371-25.2025","journal-title":"J Neurosci"},{"key":"2813_CR23","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1101\/gad.206672.112","volume":"27","author":"S Jonas","year":"2013","unstructured":"Jonas S, Weichenrieder O, Izaurralde E (2013) An unusual arrangement of two 14-3-3-like domains in the SMG5-SMG7 heterodimer is required for efficient nonsense-mediated mRNA decay. Genes Dev 27:211\u201325. https:\/\/doi.org\/10.1101\/gad.206672.112","journal-title":"Genes Dev"},{"key":"2813_CR24","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a032862","author":"ED Karousis","year":"2019","unstructured":"Karousis ED, Muhlemann O (2019) Nonsense-mediated mRNA decay begins where translation ends. Cold Spring Harb Perspect Biol. https:\/\/doi.org\/10.1101\/cshperspect.a032862","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2813_CR25","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.tibs.2022.06.003","volume":"47","author":"ED Karousis","year":"2022","unstructured":"Karousis ED, Muhlemann O (2022) The broader sense of nonsense. Trends Biochem Sci 47:921\u2013935. https:\/\/doi.org\/10.1016\/j.tibs.2022.06.003","journal-title":"Trends Biochem Sci"},{"key":"2813_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02439-3","volume":"22","author":"ED Karousis","year":"2021","unstructured":"Karousis ED, Gypas F, Zavolan M, Muhlemann O (2021) Nanopore sequencing reveals endogenous NMD-targeted isoforms in human cells. Genome Biol 22:223. https:\/\/doi.org\/10.1186\/s13059-021-02439-3","journal-title":"Genome Biol"},{"key":"2813_CR27","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/s41592-018-0051-x","volume":"15","author":"S Kim","year":"2018","unstructured":"Kim S, Scheffler K, Halpern AL, Bekritsky MA, Noh E, Kallberg M, Chen X, Kim Y, Beyter D, Krusche P, Saunders CT (2018) Strelka2: fast and accurate calling of germline and somatic variants. Nat Methods 15:591\u2013594. https:\/\/doi.org\/10.1038\/s41592-018-0051-x","journal-title":"Nat Methods"},{"key":"2813_CR28","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 (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46:310\u2013315. https:\/\/doi.org\/10.1038\/ng.2892","journal-title":"Nat Genet"},{"key":"2813_CR29","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.matbio.2014.06.003","volume":"37","author":"MN Knight","year":"2014","unstructured":"Knight MN, Hankenson KD (2014) R-spondins: novel matricellular regulators of the skeleton. Matrix Biol 37:157\u2013161. https:\/\/doi.org\/10.1016\/j.matbio.2014.06.003","journal-title":"Matrix Biol"},{"key":"2813_CR30","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/nature05676","volume":"446","author":"LF Lareau","year":"2007","unstructured":"Lareau LF, Inada M, Green RE, Wengrod JC, Brenner SE (2007) Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements. Nature 446:926\u20139. https:\/\/doi.org\/10.1038\/nature05676","journal-title":"Nature"},{"key":"2813_CR31","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1002\/ajmg.a.61317","volume":"179","author":"F Lecoquierre","year":"2019","unstructured":"Lecoquierre F, Bonnevalle A, Chadie A, Gayet C, Dumant-Forest C, Renaux-Petel M, Leca JB, Hazelzet T, Brasseur-Daudruy M, Louillet F, Muraine M, Coutant S, Quenez O, Boland A, Deleuze JF, Frebourg T, Goldenberg A, Saugier-Veber P, Guerrot AM, Nicolas G (2019) Confirmation and further delineation of the SMG9-deficiency syndrome, a rare and severe developmental disorder. Am J Med Genet A 179:2257\u20132262. https:\/\/doi.org\/10.1002\/ajmg.a.61317","journal-title":"Am J Med Genet A"},{"key":"2813_CR32","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1093\/jmcb\/mjab022","volume":"13","author":"PJ Lee","year":"2021","unstructured":"Lee PJ, Yang S, Sun Y, Guo JU (2021) Regulation of nonsense-mediated mRNA decay in neural development and disease. J Mol Cell Biol 13:269\u2013281. https:\/\/doi.org\/10.1093\/jmcb\/mjab022","journal-title":"J Mol Cell Biol"},{"key":"2813_CR33","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1002\/ajmg.a.61616","volume":"182","author":"G Lemire","year":"2020","unstructured":"Lemire G, MacDonald SK, Boycott KM (2020) SMG9-deficiency syndrome caused by a homozygous missense variant: expanding the genotypic and phenotypic spectrum of this developmental disorder. Am J Med Genet A 182:1829\u20131831. https:\/\/doi.org\/10.1002\/ajmg.a.61616","journal-title":"Am J Med Genet A"},{"key":"2813_CR34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","volume":"26","author":"H Li","year":"2010","unstructured":"Li H, Durbin R (2010) Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26:589\u2013595. https:\/\/doi.org\/10.1093\/bioinformatics\/btp698","journal-title":"Bioinformatics"},{"key":"2813_CR35","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.15252\/embj.201489947","volume":"34","author":"T Li","year":"2015","unstructured":"Li T, Shi Y, Wang P, Guachalla LM, Sun B, Joerss T, Chen YS, Groth M, Krueger A, Platzer M, Yang YG, Rudolph KL, Wang ZQ (2015) Smg6\/Est1 licenses embryonic stem cell differentiation via nonsense-mediated mRNA decay. EMBO J 34:1630\u20131647. https:\/\/doi.org\/10.15252\/embj.201489947","journal-title":"EMBO J"},{"key":"2813_CR36","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, Pritchard JK (2018) Annotation-free quantification of RNA splicing using leafcutter. Nat Genet 50:151\u2013158. https:\/\/doi.org\/10.1038\/s41588-017-0004-9","journal-title":"Nat Genet"},{"key":"2813_CR37","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.1111\/jcmm.13680","volume":"22","author":"Q Lin","year":"2018","unstructured":"Lin Q, Hou S, Guan F, Lin C (2018) HORMAD2 methylation-mediated epigenetic regulation of gene expression in thyroid cancer. J Cell Mol Med 22:4640\u20134652. https:\/\/doi.org\/10.1111\/jcmm.13680","journal-title":"J Cell Mol Med"},{"key":"2813_CR38","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"2813_CR39","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.tibs.2008.06.001","volume":"33","author":"NJ McGlincy","year":"2008","unstructured":"McGlincy NJ, Smith CW (2008) Alternative splicing resulting in nonsense-mediated mRNA decay: what is the meaning of nonsense? Trends Biochem Sci 33:385\u2013393. https:\/\/doi.org\/10.1016\/j.tibs.2008.06.001","journal-title":"Trends Biochem Sci"},{"key":"2813_CR40","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, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297\u20131303. https:\/\/doi.org\/10.1101\/gr.107524.110","journal-title":"Genome Res"},{"key":"2813_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F (2016) The Ensembl Variant Effect Predictor. Genome Biol 17:122. https:\/\/doi.org\/10.1186\/s13059-016-0974-4","journal-title":"Genome Biol"},{"key":"2813_CR42","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/s0968-0004(98)01208-0","volume":"23","author":"E Nagy","year":"1998","unstructured":"Nagy E, Maquat LE (1998) A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci 23:198\u2013199. https:\/\/doi.org\/10.1016\/s0968-0004(98)01208-0","journal-title":"Trends Biochem Sci"},{"key":"2813_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2024.104983","volume":"72","author":"D Nakato","year":"2024","unstructured":"Nakato D, Yasue Y, Matsubara K, Suzuki H, Kosaki R, Takenouchi T, Yamada M, Miya F, Takano-Shimizu T, Kosaki K (2024) De novo variants in UPF1 associated with intellectual disabilities: Human genetic and functional evidences using Drosophila model. Eur J Med Genet 72:104983. https:\/\/doi.org\/10.1016\/j.ejmg.2024.104983","journal-title":"Eur J Med Genet"},{"key":"2813_CR44","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.semcdb.2017.08.053","volume":"75","author":"S Nasif","year":"2018","unstructured":"Nasif S, Contu L, Muhlemann O (2018) Beyond quality control: the role of nonsense-mediated mRNA decay (NMD) in regulating gene expression. Semin Cell Dev Biol 75:78\u201387. https:\/\/doi.org\/10.1016\/j.semcdb.2017.08.053","journal-title":"Semin Cell Dev Biol"},{"key":"2813_CR45","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.tips.2025.01.002","volume":"46","author":"CR Neil","year":"2025","unstructured":"Neil CR, Schaening-Burgos C, Alexis MS, Reynolds DJ, Smith PG, Seiler MW, Vaillancourt FH, Agrawal AA (2025) Poison exons: tuning RNA splicing for targeted gene regulation. Trends Pharmacol Sci 46:264\u2013278. https:\/\/doi.org\/10.1016\/j.tips.2025.01.002","journal-title":"Trends Pharmacol Sci"},{"key":"2813_CR46","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1101\/gad.1525507","volume":"21","author":"JZ Ni","year":"2007","unstructured":"Ni JZ, Grate L, Donohue JP, Preston C, Nobida N, O\u2019Brien G, Shiue L, Clark TA, Blume JE, Ares M Jr. (2007) Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev 21:708\u201318. https:\/\/doi.org\/10.1101\/gad.1525507","journal-title":"Genes Dev"},{"key":"2813_CR47","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/s1097-2765(03)00443-x","volume":"12","author":"T Ohnishi","year":"2003","unstructured":"Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A, Hachiya T, Hentze MW, Anderson P, Ohno S (2003) Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Mol Cell 12:1187\u20131200. https:\/\/doi.org\/10.1016\/s1097-2765(03)00443-x","journal-title":"Mol Cell"},{"key":"2813_CR48","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","volume":"14","author":"R Patro","year":"2017","unstructured":"Patro R, Duggal G, Love MI, Irizarry RA, Kingsford C (2017) Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods 14:417\u2013419. https:\/\/doi.org\/10.1038\/nmeth.4197","journal-title":"Nat Methods"},{"key":"2813_CR49","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/nrg1726","volume":"6","author":"JC Pearson","year":"2005","unstructured":"Pearson JC, Lemons D, McGinnis W (2005) Modulating Hox gene functions during animal body patterning. Nat Rev Genet 6:893\u2013904. https:\/\/doi.org\/10.1038\/nrg1726","journal-title":"Nat Rev Genet"},{"key":"2813_CR50","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1093\/nar\/29.5.1185","volume":"29","author":"M Pertea","year":"2001","unstructured":"Pertea M, Lin X, Salzberg SL (2001) GeneSplicer: a new computational method for splice site prediction. Nucleic Acids Res 29:1185\u20131190. https:\/\/doi.org\/10.1093\/nar\/29.5.1185","journal-title":"Nucleic Acids Res"},{"key":"2813_CR51","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41431-022-01046-5","volume":"30","author":"E Rahikkala","year":"2022","unstructured":"Rahikkala E, Urpa L, Ghimire B, Topa H, Kurki MI, Koskela M, Airavaara M, Hamalainen E, Pylkas K, Korkko J, Savolainen H, Suoranta A, Bertoli-Avella A, Rolfs A, Mattila P, Daly M, Palotie A, Pietilainen O, Moilanen J, Kuismin O (2022) A novel variant in SMG9 causes intellectual disability, confirming a role for nonsense-mediated decay components in neurocognitive development. Eur J Hum Genet 30:619\u2013627. https:\/\/doi.org\/10.1038\/s41431-022-01046-5","journal-title":"Eur J Hum Genet"},{"key":"2813_CR52","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1089\/cmb.1997.4.311","volume":"4","author":"MG Reese","year":"1997","unstructured":"Reese MG, Eeckman FH, Kulp D, Haussler D (1997) Improved splice site detection in genie. J Comput Biol 4:311\u2013323. https:\/\/doi.org\/10.1089\/cmb.1997.4.311","journal-title":"J Comput Biol"},{"key":"2813_CR53","doi-asserted-by":"publisher","first-page":"R1414","DOI":"10.1016\/j.cub.2021.09.017","volume":"31","author":"N Rhind","year":"2021","unstructured":"Rhind N (2021) Cell-size control. Curr Biol 31:R1414\u2013R1420. https:\/\/doi.org\/10.1016\/j.cub.2021.09.017","journal-title":"Curr Biol"},{"key":"2813_CR54","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1261\/rna.079525.122","volume":"29","author":"PJ Russell","year":"2023","unstructured":"Russell PJ, Slivka JA, Boyle EP, Burghes AHM, Kearse MG (2023) Translation reinitiation after uORFs does not fully protect mRNAs from nonsense-mediated decay. RNA 29:735\u2013744. https:\/\/doi.org\/10.1261\/rna.079525.122","journal-title":"RNA"},{"key":"2813_CR55","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1128\/MCB.00361-08","volume":"28","author":"AL Saltzman","year":"2008","unstructured":"Saltzman AL, Kim YK, Pan Q, Fagnani MM, Maquat LE, Blencowe BJ (2008) Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay. Mol Cell Biol 28:4320\u20134330. https:\/\/doi.org\/10.1128\/MCB.00361-08","journal-title":"Mol Cell Biol"},{"key":"2813_CR56","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.ajhg.2016.02.010","volume":"98","author":"R Shaheen","year":"2016","unstructured":"Shaheen R, Anazi S, Ben-Omran T, Seidahmed MZ, Caddle LB, Palmer K, Ali R, Alshidi T, Hagos S, Goodwin L, Hashem M, Wakil SM, Abouelhoda M, Colak D, Murray SA, Alkuraya FS (2016) Mutations in SMG9, encoding an essential component of Nonsense-Mediated decay Machinery, cause a multiple congenital anomaly syndrome in humans and mice. Am J Hum Genet 98:643\u2013652. https:\/\/doi.org\/10.1016\/j.ajhg.2016.02.010","journal-title":"Am J Hum Genet"},{"key":"2813_CR57","doi-asserted-by":"publisher","first-page":"7155","DOI":"10.1093\/nar\/15.17.7155","volume":"15","author":"MB Shapiro","year":"1987","unstructured":"Shapiro MB, Senapathy P (1987) RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 15:7155\u20137174. https:\/\/doi.org\/10.1093\/nar\/15.17.7155","journal-title":"Nucleic Acids Res"},{"key":"2813_CR58","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/humu.22769","volume":"36","author":"N Sobreira","year":"2015","unstructured":"Sobreira N, Schiettecatte F, Boehm C, Valle D, Hamosh A (2015) New tools for Mendelian disease gene identification: phenodb variant analysis module; and GeneMatcher, a web-based tool for linking investigators with an interest in the same gene. Hum Mutat 36:425\u2013431. https:\/\/doi.org\/10.1002\/humu.22769","journal-title":"Hum Mutat"},{"key":"2813_CR59","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7563.2","volume":"4","author":"C Soneson","year":"2015","unstructured":"Soneson C, Love MI, Robinson MD (2015) Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res 4:1521. https:\/\/doi.org\/10.12688\/f1000research.7563.2","journal-title":"F1000Res"},{"key":"2813_CR61","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-024-07556-0","volume":"631","author":"KY Sun","year":"2024","unstructured":"Sun KY, Bai X, Chen S, Bao S, Zhang C, Kapoor M, Backman J, Joseph T, Maxwell E, Mitra G, Gorovits A, Mansfield A, Boutkov B, Gokhale S, Habegger L, Marcketta A, Locke AE, Ganel L, Hawes A, Kessler MD, Sharma D, Staples J, Bovijn J, Gelfman S, Di Gioia A, Rajagopal VM, Lopez A, Varela JR, Alegre-Diaz J, Berumen J, Tapia-Conyer R, Kuri-Morales P, Torres J, Emberson J, Collins R, Regeneron Genetics C, Partners R-MC, Cantor M, Thornton T, Kang HM, Overton JD, Shuldiner AR, Cremona ML, Nafde M, Baras A, Abecasis G, Marchini J, Reid JG, Salerno W, Balasubramanian S (2024) A deep catalogue of protein-coding variation in 983,578 individuals. Nature 631:583\u2013592. https:\/\/doi.org\/10.1038\/s41586-024-07556-0","journal-title":"Nature"},{"key":"2813_CR62","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.tig.2020.11.002","volume":"37","author":"F Supek","year":"2021","unstructured":"Supek F, Lehner B, Lindeboom RGH (2021) To NMD or not to NMD: nonsense-mediated mRNA decay in cancer and other genetic diseases. Trends Genet 37:657\u2013668. https:\/\/doi.org\/10.1016\/j.tig.2020.11.002","journal-title":"Trends Genet"},{"key":"2813_CR63","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1093\/emboj\/17.12.3484","volume":"17","author":"R Thermann","year":"1998","unstructured":"Thermann R, Neu-Yilik G, Deters A, Frede U, Wehr K, Hagemeier C, Hentze MW, Kulozik AE (1998) Binary specification of nonsense codons by splicing and cytoplasmic translation. EMBO J 17:3484\u20133494. https:\/\/doi.org\/10.1093\/emboj\/17.12.3484","journal-title":"EMBO J"},{"key":"2813_CR64","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14735","author":"Z Tumer","year":"2025","unstructured":"Tumer Z, Dalsberg J, Ronde G, Sorensen JK, Ostergaard E (2025) A novel UPF1 variant associated with a rare UPF1-related neurodevelopmental disorder. Clin Genet. https:\/\/doi.org\/10.1111\/cge.14735","journal-title":"Clin Genet"},{"key":"2813_CR65","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1128\/MCB.16.8.4273","volume":"16","author":"XZ Wang","year":"1996","unstructured":"Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ, Boorstein R, Kreibich G, Hendershot LM, Ron D (1996) Signals from the stressed endoplasmic reticulum induce C\/EBP-homologous protein (CHOP\/GADD153). Mol Cell Biol 16:4273\u20134280. https:\/\/doi.org\/10.1128\/MCB.16.8.4273","journal-title":"Mol Cell Biol"},{"key":"2813_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000702","volume":"5","author":"L Wojtasz","year":"2009","unstructured":"Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H, Boonsanay V, Eckmann CR, Cooke HJ, Jasin M, Keeney S, McKay MJ, Toth A (2009) Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet 5:e1000702. https:\/\/doi.org\/10.1371\/journal.pgen.1000702","journal-title":"PLoS Genet"},{"key":"2813_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L, Fu X, Liu S, Bo X, Yu G (2021) ClusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb) 2:100141. https:\/\/doi.org\/10.1016\/j.xinn.2021.100141","journal-title":"Innovation (Camb)"},{"key":"2813_CR68","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1073\/pnas.1502849112","volume":"112","author":"Q Yan","year":"2015","unstructured":"Yan Q, Weyn-Vanhentenryck SM, Wu J, Sloan SA, Zhang Y, Chen K, Wu JQ, Barres BA, Zhang C (2015) Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators. Proc Natl Acad Sci U S A 112:3445\u20133450. https:\/\/doi.org\/10.1073\/pnas.1502849112","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2813_CR69","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-022-01217-9","volume":"15","author":"Q Yang","year":"2022","unstructured":"Yang Q, Qin Z, Zhang Q, Yi S, Yi S, Luo J (2022) Identification of a novel compound heterozygous SMG9 variants in a Chinese family with heart and brain malformation syndrome using whole exome sequencing. BMC Med Genomics 15:67. https:\/\/doi.org\/10.1186\/s12920-022-01217-9","journal-title":"BMC Med Genomics"},{"key":"2813_CR70","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1089\/1066527041410418","volume":"11","author":"G Yeo","year":"2004","unstructured":"Yeo G, Burge CB (2004) Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 11:377\u2013394. https:\/\/doi.org\/10.1089\/1066527041410418","journal-title":"J Comput Biol"},{"key":"2813_CR71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030085","volume":"3","author":"GW Yeo","year":"2007","unstructured":"Yeo GW, Van Nostrand EL, Liang TY (2007) Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements. PLoS Genet 3:e85. https:\/\/doi.org\/10.1371\/journal.pgen.0030085","journal-title":"PLoS Genet"},{"key":"2813_CR72","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.tig.2020.08.010","volume":"37","author":"Z Yi","year":"2021","unstructured":"Yi Z, Sanjeev M, Singh G (2021) The branched nature of the nonsense-mediated mRNA decay pathway. Trends Genet 37:143\u2013159. https:\/\/doi.org\/10.1016\/j.tig.2020.08.010","journal-title":"Trends Genet"},{"key":"2813_CR73","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-3671-0","volume":"18","author":"FR Zahir","year":"2017","unstructured":"Zahir FR, Mwenifumbo JC, Chun HE, Lim EL, Van Karnebeek CDM, Couse M, Mungall KL, Lee L, Makela N, Armstrong L, Boerkoel CF, Langlois SL, McGillivray BM, Jones SJM, Friedman JM, Marra MA (2017) Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability. BMC Genomics 18:403. https:\/\/doi.org\/10.1186\/s12864-017-3671-0","journal-title":"BMC Genomics"},{"key":"2813_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.111972","volume":"28","author":"S Zhu","year":"2025","unstructured":"Zhu S, Huo S, He W, Huang C, Zhang J, Jiang X, Qian Y, Chen C, Dai ZM, Yang X, Qiu M, Li T, Zhu XJ (2025) Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development. iScience 28:111972. https:\/\/doi.org\/10.1016\/j.isci.2025.111972","journal-title":"iScience"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-025-02813-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00439-025-02813-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-025-02813-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:31:27Z","timestamp":1772191887000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00439-025-02813-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":73,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2813"],"URL":"https:\/\/doi.org\/10.1007\/s00439-025-02813-2","relation":{},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"assertion":[{"value":"30 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Hamburg Medical Chamber (PV7038-4438-BO-ff; Hamburg, Germany).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from the parents.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images in Fig.\u00a01a and Supplementary Fig.\u00a01.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"26"}}