{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:45:32Z","timestamp":1777355132250,"version":"3.51.4"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["Higher Education Dialogue with the Muslim World"],"award-info":[{"award-number":["Higher Education Dialogue with the Muslim World"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR\u20102715"],"award-info":[{"award-number":["FOR\u20102715"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["grant He5415\/7-1"],"award-info":[{"award-number":["grant He5415\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurogenetics"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ataxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine\/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two <jats:italic>ATM<\/jats:italic> gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as pathogenic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.<\/jats:p>","DOI":"10.1007\/s10048-021-00639-4","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T10:03:18Z","timestamp":1617012198000},"page":"143-147","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evidence for pathogenicity of variant ATM Val1729Leu in a family with ataxia telangiectasia"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-5907","authenticated-orcid":false,"given":"Ali S.","family":"Shalash","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"R\u00f6sler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-767X","authenticated-orcid":false,"given":"Mohamed","family":"Salama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Pendziwiat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie H.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-0281","authenticated-orcid":false,"given":"Franziska","family":"Hopfner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-8113","authenticated-orcid":false,"given":"Gregor","family":"Kuhlenb\u00e4umer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"issue":"8","key":"639_CR1","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1002\/mds.27319","volume":"33","author":"A Levy","year":"2018","unstructured":"Levy A, Lang AE (2018) Ataxia-telangiectasia: a review of movement disorders, clinical features, and genotype correlations. Mov Disord 33(8):1238\u20131247. https:\/\/doi.org\/10.1002\/mds.27319","journal-title":"Mov Disord"},{"issue":"1","key":"639_CR2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","volume":"11","author":"C Rothblum-Oviatt","year":"2016","unstructured":"Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM (2016) Ataxia telangiectasia: a review. Orphanet J Rare Dis 11(1):159. https:\/\/doi.org\/10.1186\/s13023-016-0543-7","journal-title":"Orphanet J Rare Dis"},{"issue":"5218","key":"639_CR3","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1126\/science.7792600","volume":"268","author":"K Savitsky","year":"1995","unstructured":"Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 268(5218):1749\u20131753. https:\/\/doi.org\/10.1126\/science.7792600","journal-title":"Science."},{"issue":"7","key":"639_CR4","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1136\/jmedgenet-2012-100918","volume":"49","author":"X Chang","year":"2012","unstructured":"Chang X, Wang K (2012) wANNOVAR: annotating genetic variants for personal genomes via the web. J Med Genet 49(7):433\u2013436. https:\/\/doi.org\/10.1136\/jmedgenet-2012-100918","journal-title":"J Med Genet"},{"issue":"3","key":"639_CR5","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'Roak BJ, Cooper GM, Shendure J (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46(3):310\u2013315. https:\/\/doi.org\/10.1038\/ng.2892","journal-title":"Nat Genet"},{"issue":"4","key":"639_CR6","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. https:\/\/doi.org\/10.1038\/nmeth.2890","journal-title":"Nat Methods"},{"issue":"4","key":"639_CR7","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","volume":"7","author":"IA Adzhubei","year":"2010","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248\u2013249. https:\/\/doi.org\/10.1038\/nmeth0410-248","journal-title":"Nat Methods"},{"issue":"10","key":"639_CR8","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s00439-020-02199-3","volume":"139","author":"PD Stenson","year":"2020","unstructured":"Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN (2020) The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting. Hum Genet 139(10):1197\u20131207. https:\/\/doi.org\/10.1007\/s00439-020-02199-3","journal-title":"Hum Genet"},{"issue":"D1","key":"639_CR9","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","volume":"46","author":"MJ Landrum","year":"2018","unstructured":"Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Jang W, Karapetyan K, Katz K, Liu C, Maddipatla Z, Malheiro A, McDaniel K, Ovetsky M, Riley G, Zhou G, Holmes JB, Kattman BL, Maglott DR (2018) ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res 46(D1):D1062\u2013D10D7. https:\/\/doi.org\/10.1093\/nar\/gkx1153","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"639_CR10","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1002\/humu.21438","volume":"32","author":"IF Fokkema","year":"2011","unstructured":"Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011) LOVD v.2.0: the next generation in gene variant databases. Hum Mutat 32(5):557\u2013563. https:\/\/doi.org\/10.1002\/humu.21438","journal-title":"Hum Mutat"},{"issue":"6","key":"639_CR11","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/mgg3.98","volume":"2","author":"MJ Podralska","year":"2014","unstructured":"Podralska MJ, Stembalska A, \u015al\u0119zak R, Lewandowicz-Uszy\u0144ska A, Pietrucha B, Ko\u0142tan S, Wigowska-Sowi\u0144ska J, Pilch J, Mosor M, Zi\u00f3\u0142kowska-Suchanek I, Dzikiewicz-Krawczyk A, S\u0142omski R (2014) Ten new ATM alterations in Polish patients with ataxia-telangiectasia. Mol Genet Genomic Med 2(6):504\u2013511. https:\/\/doi.org\/10.1002\/mgg3.98","journal-title":"Mol Genet Genomic Med"},{"issue":"Pt 6","key":"639_CR12","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/j.1529-8817.2005.00199.x","volume":"69","author":"M Mitui","year":"2005","unstructured":"Mitui M, Bernatowska E, Pietrucha B, Piotrowska-Jastrzebska J, Eng L, Nahas S, Teraoka S, Sholty G, Purayidom A, Concannon P, Gatti RA (2005) ATM gene founder haplotypes and associated mutations in Polish families with ataxia-telangiectasia. Ann Hum Genet 69(Pt 6):657\u2013664. https:\/\/doi.org\/10.1111\/j.1529-8817.2005.00199.x","journal-title":"Ann Hum Genet"},{"issue":"4","key":"639_CR13","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1155\/2006\/740493","volume":"22","author":"M Magliozzi","year":"2006","unstructured":"Magliozzi M, Piane M, Torrente I, Sinibaldi L, Rizzo G, Savio C, Lulli P, de Luca A, Dallapiccola B, Chessa L (2006) DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations. Dis Markers 22(4):257\u2013264. https:\/\/doi.org\/10.1155\/2006\/740493","journal-title":"Dis Markers"},{"issue":"4","key":"639_CR14","doi-asserted-by":"publisher","first-page":"e34573","DOI":"10.1371\/journal.pone.0034573","volume":"7","author":"C George Priya Doss","year":"2012","unstructured":"George Priya Doss C, Rajith B (2012) Computational refinement of functional single nucleotide polymorphisms associated with ATM gene. PLoS One 7(4):e34573. https:\/\/doi.org\/10.1371\/journal.pone.0034573","journal-title":"PLoS One"},{"issue":"5","key":"639_CR15","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1001\/jamaneurol.2017.5121","volume":"75","author":"M Coutelier","year":"2018","unstructured":"Coutelier M, Hammer MB, Stevanin G, Monin ML, Davoine CS, Mochel F, Labauge P, Ewenczyk C, Ding J, Gibbs JR, Hannequin D, Melki J, Toutain A, Laugel V, Forlani S, Charles P, Broussolle E, Thobois S, Afenjar A, Anheim M, Calvas P, Castelnovo G, de Broucker T, Vidailhet M, Moulignier A, Ghnassia RT, Tallaksen C, Mignot C, Goizet C, le Ber I, Ollagnon-Roman E, Pouget J, Brice A, Singleton A, Durr A, for the Spastic Paraplegia and Ataxia Network (2018) Efficacy of exome-targeted capture sequencing to detect mutations in known cerebellar ataxia genes. JAMA Neurol 75(5):591\u2013599. https:\/\/doi.org\/10.1001\/jamaneurol.2017.5121","journal-title":"JAMA Neurol"},{"key":"639_CR16","doi-asserted-by":"publisher","unstructured":"Paucar M, Taylor AMR, Hadjivassiliou M, Fogel BL, Svenningsson P (2019) Progressive ataxia with elevated alpha-fetoprotein: diagnostic issues and review of the literature. Tremor Other Hyperkinet Mov (NY) 9. https:\/\/doi.org\/10.7916\/tohm.v0.708","DOI":"10.7916\/tohm.v0.708"}],"container-title":["neurogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10048-021-00639-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10048-021-00639-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10048-021-00639-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T08:20:36Z","timestamp":1620894036000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10048-021-00639-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["639"],"URL":"https:\/\/doi.org\/10.1007\/s10048-021-00639-4","relation":{},"ISSN":["1364-6745","1364-6753"],"issn-type":[{"value":"1364-6745","type":"print"},{"value":"1364-6753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]},"assertion":[{"value":"29 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2021","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 present study was conducted in accordance with the principles of the Declaration of Helsinki and approved by local Ethics Committee of Mansoura University (RP\/42), Egypt and Technical University of Munich (203\/15s), Germany.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained for all participants. If the participant was minor or incapable, consent was given by the legal custodian.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All participants gave their consent for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}