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AGS has been associated with pathogenic variants in nine genes: <jats:italic>TREX1<\/jats:italic>, <jats:italic>RNASEH2B<\/jats:italic>, <jats:italic>RNASEH2C<\/jats:italic>, <jats:italic>RNASEH2A<\/jats:italic>, <jats:italic>SAMHD1<\/jats:italic>, <jats:italic>ADAR<\/jats:italic>, <jats:italic>IFIH1<\/jats:italic>, <jats:italic>LSM11<\/jats:italic>, and <jats:italic>RNU7<\/jats:italic>\u2010<jats:italic>1<\/jats:italic>. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and\/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic\/likely pathogenic variants in the known genes. One of the genes associated with AGS, <jats:italic>SAMHD1<\/jats:italic>, has also been associated with a spectrum of cerebrovascular diseases, including moyamoya disease (MMD). In this report, we describe a 31\u2010year\u2010old male referred to genetics for MMD since childhood who lacked the hallmark features of AGS patients but was found to have compound heterozygous <jats:italic>SAMHD1<\/jats:italic> variants. He later developed mitral valve insufficiency due to recurrent chordal rupture and ultimately underwent a heart transplant at 37\u2009years of age. Thus, these data suggest that <jats:italic>SAMHD1<\/jats:italic> pathogenic variants can cause MMD without typical AGS symptoms and support that <jats:italic>SAMHD1<\/jats:italic> should be assessed in MMD patients even in the absence of AGS features.<\/jats:p>","DOI":"10.1002\/ajmg.a.63486","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T16:45:34Z","timestamp":1701535534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp><i>SAMHD1<\/i><\/scp> compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of <scp>Aicardi\u2013Gouti\u00e8res<\/scp> syndrome"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2271-6939","authenticated-orcid":false,"given":"Aamuktha R.","family":"Karla","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Pinard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura L.","family":"Boerio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Hemelsoet","sequence":"additional","affiliation":[{"name":"Department of Neurology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Tavernier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Pediatrics, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"De Pauw","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Vereecke","sequence":"additional","affiliation":[{"name":"Department of Radiology Ghent University Hospital  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Fraser","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongchuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-4205","authenticated-orcid":false,"given":"Bert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Ghent Ghent University Hospital  Ghent Belgium"},{"name":"Department of Biomolecular Medicine Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, McGovern Medical School University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410150109"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.30637\/2018.16-030"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1739131"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801213115"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106457"},{"key":"e_1_2_8_7_1","volume-title":"GeneReviews","author":"Crow Y. 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