{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:12:27Z","timestamp":1790467947556,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T00:00:00Z","timestamp":1410134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C1016\/A14346"],"award-info":[{"award-number":["C1016\/A14346"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>\n                    Ataxia telangiectasia (A\u2010T) is a rare recessively inherited disorder resulting in a progressive neurological decline. It is caused by biallelic mutation of the\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\n                    <\/jats:italic>\n                    gene that encodes a 370\n                    <jats:styled-content style=\"fixed-case\">kDa<\/jats:styled-content>\n                    serine\/threonine protein kinase responsible for phosphorylating many target proteins.\n                    <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\n                    is activated by auto(trans)phosphorylation in response to\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    double strand breaks and leads to the activation of cell cycle checkpoints and either\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    repair or apoptosis as part of the cellular response to\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    damage. The allelic heterogeneity in A\u2010T is striking. While the majority of mutations are truncating, leading to instability and loss of the\n                    <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\n                    protein from the allele, a significant proportion of patients carry one of a small number of mutations that are either missense or leaky splice site mutations resulting in retention of some\n                    <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\n                    with activity. The allelic heterogeneity in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\n                    <\/jats:italic>\n                    , therefore, results in an equally striking clinical heterogeneity. There is also locus heterogeneity because mutation of the\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">MRE11<\/jats:styled-content>\n                    <\/jats:italic>\n                    gene can cause an obvious A\u2010T like disorder both clinically and also at the cellular level and mutation of the\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">RNF168<\/jats:styled-content>\n                    <\/jats:italic>\n                    gene results in a much milder clinical phenotype, neurologically, with the major clinical feature being an immunological defect.\n                  <\/jats:p>","DOI":"10.1111\/cge.12453","type":"journal-article","created":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T13:38:09Z","timestamp":1404740289000},"page":"199-208","source":"Crossref","is-referenced-by-count":97,"title":["Ataxia telangiectasia: more variation at clinical and cellular levels"],"prefix":"10.1111","volume":"87","author":[{"given":"A.M.R.","family":"Taylor","sequence":"first","affiliation":[{"name":"School of Cancer Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Lam","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.I.","family":"Last","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.J.","family":"Byrd","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3546"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3231"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.053"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.266"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.21.4.526"},{"key":"e_1_2_10_7_1","first-page":"347","volume-title":"Handbook of clinical neurology. Hereditary neuropathies and spinocerebellar atrophies","author":"Sedgwick RP","year":"1991"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.7.1505"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01796-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81547-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-189"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.12.046"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03684.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.09.35"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000330335"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.06.060"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(00)70106-5"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-23"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20738"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21277"},{"key":"e_1_2_10_21_1","first-page":"90","article-title":"Ataxia telangiectasia and mechanical ventilation: a word of caution","volume":"13","author":"Verhagen MMM","year":"2009","journal-title":"Neth J Crit Care"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.094268"},{"key":"e_1_2_10_23_1","first-page":"169","article-title":"Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals","volume":"82","author":"Woods CG","year":"1992","journal-title":"Q J Med"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-008-0055-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21034"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210809"},{"key":"e_1_2_10_27_1","first-page":"320","article-title":"Mutations associated with variant phenotypes in ataxia\u2010telangiectasia","volume":"59","author":"McConville CM","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/301706"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20139"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000224878.22821.23"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af33bd"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22016"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2013.08.013"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182494d51"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103160200"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07281.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.534"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25236"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31853"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110217"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh221"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2010.12.002"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81174-5"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi027"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.02.037"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt368"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708408104"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.042"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.18"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.03.052"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112263252602"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1329"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.2.121"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji141"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2919"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2011.02.007"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/2041-9414-1-9"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12453","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T01:00:47Z","timestamp":1696294847000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,8]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/cge.12453"],"URL":"https:\/\/doi.org\/10.1111\/cge.12453","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,8]]}}}