{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:32:31Z","timestamp":1790951551201,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A minority of breast cancer (BC) patients suffer from severe reaction to adjuvant radiotherapy (RT). Although deficient DNA double\u2010strand break repair is considered the main basis for the reactions, pretreatment identification of high\u2010risk patients has been challenging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To retrospectively determine the etiology of severe local reaction to RT in a 39\u2010year\u2010old woman with BC, we performed next\u2010generation sequencing followed by further clinical and functional studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a \u22124 intronic variant (c.2251\u20104A&gt;G) in trans with a synonymous (c.3576G&gt;A) variant affecting the <jats:italic>ATM<\/jats:italic> DNA\u2010repair gene (NG_009830.1, NM_000051.3) which is linked to autosomal recessive ataxia\u2013telangiectasia (A\u2013T). We verified abnormal transcripts resulting from both variants, next to a minor wild\u2010type transcript leading to a residual ATM kinase activity and genomic instability. Follow\u2010up examination of the patient revealed no classic sign of A\u2013T but previously unnoticed head dystonia and mild dysarthria, a family history of BC and late\u2010onset ataxia segregating with the variants. Additionally, her serum level of alpha\u2010fetoprotein (AFP) was elevated similar to A\u2013T patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Considering the variable presentations of A\u2013T and devastating impact of severe reactions to RT, we suggest a routine measurement of AFP in RT\u2010candidate BC patients followed by next\u2010generation sequencing with special attention to non\u2010canonical splice site and synonymous variants in <jats:italic>ATM<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1409","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T04:51:10Z","timestamp":1596516670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Severe reaction to radiotherapy provoked by hypomorphic germline mutations in <i>ATM<\/i> (ataxia\u2013telangiectasia mutated 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