{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:59:54Z","timestamp":1782489594191,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ataxia\u2010telangiectasia (A\u2010T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, ocular apraxia, immunodeficiency, telangiectasia, elevated serum \u03b1\u2010fetoprotein concentration, radiosensitivity and cancer predisposition. Classical A\u2010T is caused by biallelic variants on <jats:italic>ATM<\/jats:italic> (<jats:italic>ataxia telangiectasia mutated<\/jats:italic>) gene, leading to a loss of function of the protein kinase ATM, involved in DNA damage repair. Atypical presentations can be found in A\u2010T\u2010like disease or in Nijmegen breakage syndrome, caused by deficiency of mre11 or nibrin proteins, respectively. In this report, we present the genetic characterization of a 4\u2010year\u2010old female with clinical diagnosis of A\u2010T. Next\u2010generation sequencing (NGS) revealed two novel heterozygous mutations in the <jats:italic>ATM<\/jats:italic> gene: a single\u2010nucleotide variant (SNV) at exon 47 (NM_000051.3:c.6899G\u00a0&gt;\u00a0C; p.Trp2300Ser) and \u223c90\u00a0kb genomic duplication spanning exons 17\u201361, NG_009830.1:g.(41245_49339)_(137044_147250)dup. These findings were validated by Sanger sequencing and MLPA (multiplex ligation\u2010dependent probe amplification) analysis respectively. Familial segregation study confirmed that the two variants are inherited, and the infant is a compound heterozygote. Thus, our study expands the spectrum of <jats:italic>ATM<\/jats:italic> pathogenic variants and demonstrates the utility of targeted NGS in the detection of copy number variation.<\/jats:p>","DOI":"10.1111\/ahg.12312","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T01:22:38Z","timestamp":1553044958000},"page":"266-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Two novel variants in the <i>ATM<\/i> gene causing ataxia\u2010telangiectasia, including a duplication of 90\u00a0kb: Utility of targeted next\u2010generation sequencing in detection of copy number variation"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-5992","authenticated-orcid":false,"given":"Samuel","family":"Martin\u2010Rodriguez","sequence":"first","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Calvo\u2010Ferrer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Ortega\u2010Unanue","sequence":"additional","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Samaniego\u2010Jimenez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pilar","family":"Sanz\u2010Izquierdo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Bernardo\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Diagnostics Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.21.4.526"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2005.11.022"},{"issue":"1","key":"e_1_2_8_4_1","first-page":"24","article-title":"ATM mutations in B\u2010cell chronic lymphocytic leukemia","volume":"59","author":"Bullrich F.","year":"1999","journal-title":"Cancer Research"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30498"},{"issue":"1","key":"e_1_2_8_6_1","first-page":"10","article-title":"Large genomic mutations within the ATM gene detected by MLPA, including a duplication of 41 kb from 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