{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:04:21Z","timestamp":1791443061220,"version":"4.3.3"},"reference-count":11,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T00:00:00Z","timestamp":1404259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R24AG042328"],"award-info":[{"award-number":["R24AG042328"]}]},{"DOI":"10.13039\/100000863","name":"Ellison Medical Foundation","doi-asserted-by":"crossref","award":["AG-SS-1915-07"],"award-info":[{"award-number":["AG-SS-1915-07"]}],"id":[{"id":"10.13039\/100000863","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>We describe a 28\u2010year\u2010old Turkish man with consanguineous parents who presented with an aged appearance with prematurely gray hair and scleroderma\u2010like skin, spastic paraplegia, and apparent disability. The proband and each of his parents were heterozygous for a mutation in <jats:italic>WRN<\/jats:italic>, which could not explain his symptoms. Exome sequencing of the proband's blood DNA showed a homozygous c.626\u20101G\u2009&gt;\u2009C mutation in intron 5 of the <jats:italic>SAMHD1<\/jats:italic> gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi\u2010Goutieres syndrome. The RNA studies confirmed aberrant splicing of exon 6, and family studies showed that both parents are heterozygous for this mutation. We conclude that mutations in <jats:italic>SAMHD1<\/jats:italic> \u2010 in addition to causing an early\u2010onset form of encephalopathy in Aicardi\u2010Goutieres syndrome \u2010 may present with modest signs of accelerated aging similar to Werner syndrome. The extent to which heterozygosity at the <jats:italic>WRN<\/jats:italic> locus may modify the effect of biallelic <jats:italic>SAMHD1<\/jats:italic> mutations is unknown. It is conceivable that synergistic effects of these two mutations might be responsible for the unusual phenotype. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36664","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T18:30:53Z","timestamp":1404325853000},"page":"2510-2513","source":"Crossref","is-referenced-by-count":18,"title":["Atypical Aicardi\u2010Goutieres syndrome: Is the <i>WRN<\/i> locus a modifier?"],"prefix":"10.1002","volume":"164","author":[{"given":"Davor","family":"Lessel","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidisha","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuki","family":"Hisama","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Kaymakamzade","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculty of Medicine Near East University Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulay","family":"Nurlu","sequence":"additional","affiliation":[{"name":"Department of Neurology Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Gursoy\u2010\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Department of Neurology Hacettepe University Ankara Turkey"},{"name":"Institute of Neurological Sciences and Psychiatry Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"},{"name":"Center for Molecular Medicine Cologne University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kubisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.431148"},{"key":"e_1_2_6_3_1","article-title":"SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage","author":"Clifford 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