{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:56:01Z","timestamp":1775696161874,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>We report a family in which two brothers had an undiagnosed genetic disorder comprised of dysmorphic features, microcephaly, severe intellectual disability (non\u2010verbal), mild anemia, and cryptorchidism. Both developed osteosarcoma. Trio exome sequencing (using blood samples from the younger brother and both parents) was performed and a nonsense NM_000489.4:c.7156C&gt;T (p.Arg2386*) mutation in the <jats:italic>ATRX<\/jats:italic> gene was identified in the proband (hemizygous) and in the mother's peripheral blood DNA (heterozygous). The mother is healthy, does not exhibit any clinical manifestations of ATR\u2010X syndrome and there was no family history of cancer. The same hemizygous pathogenic variant was confirmed in the affected older brother's skin tissue by subsequent Sanger sequencing. Chromosomal microarray studies of both brothers\u2019 osteosarcomas revealed complex copy number alterations consistent with the clinical diagnosis of osteosarcoma. Recently, somatic mutations in the <jats:italic>ATRX<\/jats:italic> gene have been observed as recurrent alterations in both osteosarcoma and brain tumors. However, it is unclear if there is any association between osteosarcoma and germline <jats:italic>ATRX<\/jats:italic> mutations, specifically in patients with constitutional ATR\u2010X syndrome. This is the first report of osteosarcoma diagnosed in two males with ATR\u2010X syndrome, suggesting a potential increased risk for cancer in patients with this disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38184","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T16:21:09Z","timestamp":1490718069000},"page":"1390-1395","source":"Crossref","is-referenced-by-count":31,"title":["Inherited germline <i>ATRX<\/i> mutation in two brothers with ATR\u2010X syndrome and osteosarcoma"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-3538","authenticated-orcid":false,"given":"Jianling","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Quindipan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Parham","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California"},{"name":"Department of Pediatrics, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lishuang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ruble","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moiz","family":"Bootwalla","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis T.","family":"Maglinte","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowu","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sulagna C.","family":"Saitta","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn A.","family":"Biegel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Center for Personalized Medicine, Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Mascarenhas","sequence":"additional","affiliation":[{"name":"Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles Los Angeles California"},{"name":"Department of Pediatrics, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(89)90169-6"},{"issue":"4","key":"e_1_2_8_3_1","first-page":"e93409","article-title":"Massively parallel sequencing of patients with intellectual disability, congenital anomalies and\/or autism spectrum disorders with a targeted gene panel","volume":"9","author":"Brett M.","year":"2014","journal-title":"Public Library of 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