{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:02:57Z","timestamp":1792612977975,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"11-12","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["12060187"],"award-info":[{"award-number":["12060187"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["12060187"],"award-info":[{"award-number":["12060187"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["12060187"],"award-info":[{"award-number":["12060187"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["12060187"],"award-info":[{"award-number":["12060187"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["12060187"],"award-info":[{"award-number":["12060187"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Centre Egypt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Neurosci"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Otofaciocervical syndrome (OTFCS) is a rare genetic disorder of both autosomal recessive and autosomal dominant patterns of inheritance. It is caused by biallelic or monoallelic mutations in <jats:italic>PAX1<\/jats:italic> or <jats:italic>EYA1<\/jats:italic> genes, respectively. Here, we report an OTFCS2 female patient of 1st consanguineous healthy parents. She manifested facial dysmorphism, hearing loss, intellectual disability (ID), and delayed language development (DLD) as the main clinical phenotype. The novel homozygous variant c.1212dup (p.Gly405Argfs*51) in the <jats:italic>PAX1<\/jats:italic> gene was identified by whole exome sequencing (WES), and family segregation confirmed the heterozygous status of the mutation in the parents using the Sanger sequencing. The study recorded a novel <jats:italic>PAX1<\/jats:italic> variant representing the sixth report of OTFCS2 worldwide and the first Egyptian study expanding the geographic area where the disorder was confined.<\/jats:p>","DOI":"10.1007\/s12031-023-02170-7","type":"journal-article","created":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T07:01:52Z","timestamp":1699081312000},"page":"976-982","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Truncating Mutation in PAX1 Gene Causes Otofaciocervical Syndrome Without Immunodeficiency"],"prefix":"10.1007","volume":"73","author":[{"given":"Nagham M.","family":"Elbagoury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa F.","family":"Abdel-Aleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessam E.","family":"Sharaf-Eldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy A.","family":"Ashaat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona L.","family":"Esswai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,4]]},"reference":[{"issue":"4","key":"2170_CR1","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1242\/dev.091785","volume":"141","author":"JA Blake","year":"2014","unstructured":"Blake JA, Ziman MR (2014) Pax genes: regulators of lineage specification and progenitor cell maintenance. Development 141(4):737\u2013751","journal-title":"Development"},{"issue":"10","key":"2170_CR2","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1038\/s41431-022-01154-2","volume":"30","author":"S Carter","year":"2022","unstructured":"Carter S, Fellows BJ, Gibson K, Bicknell LS (2022) Extending the PAX1 spectrum: a dominantly inherited variant causes oculo-auriculo-vertebral syndrome. Eur J Hum Genet 30(10):1178\u20131181","journal-title":"Eur J Hum Genet"},{"issue":"11","key":"2170_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102592","volume":"298","author":"CM Embree","year":"2022","unstructured":"Embree CM, Abu-Alhasan R, Singh G (2022) Features and factors that dictate if terminating ribosomes cause or counteract nonsense-mediated mRNA decay. J Biol Chem 298(11):102592","journal-title":"J Biol Chem"},{"key":"2170_CR4","doi-asserted-by":"crossref","unstructured":"Gana S, Valetto A, Toschi B, Sardelli I, Cappelli S, Peroni D, Bertini V (2019) Familial interstitial 6q23.2 deletion including EYA4 associated with otofaciocervical syndrome. Front Gene\u00a010: 650","DOI":"10.3389\/fgene.2019.00650"},{"key":"2170_CR5","unstructured":"Karczewski K, Francioli L (2017) The genome aggregation database (gnomAD). MacArthur Lab\u00a01\u201310"},{"issue":"D1","key":"2170_CR6","doi-asserted-by":"publisher","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","volume":"44","author":"MJ Landrum","year":"2016","unstructured":"Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44(D1):D862\u2013D868","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"2170_CR7","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1093\/bioinformatics\/btac188","volume":"38","author":"L Nie","year":"2022","unstructured":"Nie L, Quan L, Wu T, He R, Lyu Q (2022) TransPPMP: predicting pathogenicity of frameshift and non-sense mutations by a transformer based on protein features. Bioinformatics 38(10):2705\u20132711","journal-title":"Bioinformatics"},{"issue":"11","key":"2170_CR8","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.tig.2021.05.002","volume":"37","author":"A Nishiyama","year":"2021","unstructured":"Nishiyama A, Nakanishi M (2021) Navigating the DNA methylation landscape of cancer. Trends Genet 37(11):1012\u20131027","journal-title":"Trends Genet"},{"issue":"6","key":"2170_CR9","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1111\/cge.13085","volume":"92","author":"I Paganini","year":"2017","unstructured":"Paganini I, Sestini R, Capone G, Putignano A, Contini E, Giotti I, Gensini F, Marozza A, Barilaro A, Porfirio B (2017) A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency. Clin Genet 92(6):664\u2013668","journal-title":"Clin Genet"},{"issue":"5","key":"2170_CR10","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1002\/ajmg.a.38659","volume":"176","author":"SJ Patil","year":"2018","unstructured":"Patil SJ, Das Bhowmik A, Bhat V, Satidevi Vineeth V, Vasudevamurthy R, Dalal A (2018) Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene. Am J Med Genet A 176(5):1200\u20131206","journal-title":"Am J Med Genet A"},{"key":"2170_CR11","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s00439-013-1337-9","volume":"132","author":"E Pohl","year":"2013","unstructured":"Pohl E, Aykut A, Beleggia F, Karaca E, Durmaz B, Keupp K, Arslan E, Onay MP, Yigit G, \u00d6zkinay F (2013) A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome. Hum Genet 132:1311\u20131320","journal-title":"Hum Genet"},{"issue":"7229","key":"2170_CR12","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nature07716","volume":"457","author":"RT Pollard","year":"2009","unstructured":"Pollard RT, Salter I, Sanders RJ, Lucas MI, Moore CM, Mills RA, Statham PJ, Allen JT, Baker AR, Bakker DC (2009) Southern Ocean deep-water carbon export enhanced by natural iron fertilization. Nature 457(7229):577\u2013580","journal-title":"Nature"},{"issue":"D1","key":"2170_CR13","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 (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47(D1):D886\u2013D894","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"2170_CR14","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1136\/archdischild-2014-306425","volume":"100","author":"L Rivers","year":"2015","unstructured":"Rivers L, Gaspar HB (2015) Severe combined immunodeficiency: recent developments and guidance on clinical management. Arch Dis Child 100(7):667\u2013672","journal-title":"Arch Dis Child"},{"issue":"4","key":"2170_CR15","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nmeth.2890","volume":"11","author":"JM Schwarz","year":"2014","unstructured":"Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11(4):361\u2013362","journal-title":"Nat Methods"},{"issue":"9","key":"2170_CR16","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/ng.3592","volume":"48","author":"EM Scott","year":"2016","unstructured":"Scott EM, Halees A, Itan Y, Spencer EG, He Y, Azab MA, Gabriel SB, Belkadi A, Boisson B, Abel L (2016) Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery. Nat Genet 48(9):1071\u20131076","journal-title":"Nat Genet"},{"issue":"7","key":"2170_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104523","volume":"65","author":"C Sherlaw-Sturrock","year":"2022","unstructured":"Sherlaw-Sturrock C, Austin T, Baptista J, Gilmour K, Naik S (2022) Dysmorphism and immunodeficiency-one of the differential diagnoses is PAX1 related otofaciocervical syndrome type 2. Eur J Med Genet 65(7):104523","journal-title":"Eur J Med Genet"},{"issue":"6","key":"2170_CR18","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/humu.10212","volume":"21","author":"PD Stenson","year":"2003","unstructured":"Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN (2003) Human Gene Mutation Database (HGMD\u00ae): 2003 update. Hum Mutat 21(6):577\u2013581","journal-title":"Hum Mutat"},{"issue":"2","key":"2170_CR19","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1006\/dbio.2001.0342","volume":"236","author":"D-m Su","year":"2001","unstructured":"Su D-m, Ellis S, Napier A, Lee K, Manley NR (2001) Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Dev Biol 236(2):316\u2013329","journal-title":"Dev Biol"},{"key":"2170_CR20","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00439-020-02212-9","volume":"140","author":"B Thompson","year":"2021","unstructured":"Thompson B, Davidson EA, Liu W, Nebert DW, Bruford EA, Zhao H, Dermitzakis ET, Thompson DC, Vasiliou V (2021) Overview of PAX gene family: analysis of human tissue-specific variant expression and involvement in human disease. Hum Genet 140:381\u2013400","journal-title":"Hum Genet"},{"key":"2170_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variations from next-generation sequencing data. Nucl Acids Res 38:e164","journal-title":"Nucl Acids Res"},{"key":"2170_CR22","doi-asserted-by":"crossref","unstructured":"Wu W, Kong X, Jia Y, Jia Y, Ou W, Dai C, Li G, Gao R (2022) An overview of PAX1: expression, function and regulation in development and diseases. Front Cell Dev Biol\u00a010","DOI":"10.3389\/fcell.2022.1051102"},{"key":"2170_CR23","doi-asserted-by":"crossref","unstructured":"Yamazaki Y, Urrutia R, Franco LM, Giliani S, Zhang K, Alazami AM, Dobbs AK, Masneri S, Joshi A, Otaizo-Carrasquero F (2020) PAX1 is essential for development and function of the human thymus. Sci Immunol\u00a05(44): eaax1036","DOI":"10.1126\/sciimmunol.aax1036"},{"key":"2170_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2013-14-3-r23","volume":"14","author":"H Zhao","year":"2013","unstructured":"Zhao H, Yang Y, Lin H, Zhang X, Mort M, Cooper DN, Liu Y, Zhou Y (2013) DDIG-in: discriminating between disease-associated and neutral non-frameshifting micro-indels. Genome Biol 14:1\u201313","journal-title":"Genome Biol"}],"container-title":["Journal of Molecular Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12031-023-02170-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12031-023-02170-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12031-023-02170-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T02:10:18Z","timestamp":1703815818000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12031-023-02170-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,4]]},"references-count":24,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["2170"],"URL":"https:\/\/doi.org\/10.1007\/s12031-023-02170-7","relation":{},"ISSN":["0895-8696","1559-1166"],"issn-type":[{"value":"0895-8696","type":"print"},{"value":"1559-1166","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,4]]},"assertion":[{"value":"27 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Helsinki\u2019s guiding principles were followed during the study. The study has been granted approval by the NRC Medical Research Ethics Committee (ID: 19261). After fully explaining the study to parents, their written agreement was acquired.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interest"}}]}}