{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:09:50Z","timestamp":1791317390296,"version":"4.3.1"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T00:00:00Z","timestamp":1465430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["1U41HG006834"],"award-info":[{"award-number":["1U41HG006834"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K12 NS079414\u201002"],"award-info":[{"award-number":["K12 NS079414\u201002"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Mutations in <jats:italic>BRAT1<\/jats:italic>, encoding BRCA1\u2010associated ATM activator 1, are associated with a severe phenotype known as rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL; OMIM # 614498), characterized by intractable seizures, hypertonia, autonomic instability, and early death. We expand the phenotypic spectrum of <jats:italic>BRAT1<\/jats:italic> related disorders by reporting on four individuals with various <jats:italic>BRAT1<\/jats:italic> mutations resulting in clinical severity that is either mild or moderate compared to the severe phenotype seen in RMFSL. Representing mild severity are three individuals (Patients 1\u20133), who are girls (including two sisters, Patients 1\u20132) between 4 and 10 years old, with subtle dysmorphisms, intellectual disability, ataxia or dyspraxia, and cerebellar atrophy on brain MRI; additionally, Patient 3 has well\u2010controlled epilepsy and microcephaly. Representing moderate severity is a 15\u2010month\u2010old boy (Patient 4) with severe global developmental delay, refractory epilepsy, microcephaly, spasticity, hyperkinetic movements, dysautonomia, and chronic lung disease. In contrast to RMFSL, his seizure onset occurred later at 4 months of age, and he is still alive. All four of the individuals have compound heterozygous <jats:italic>BRAT1<\/jats:italic> mutations discovered via whole exome sequencing: c.638dupA (p.Val214Glyfs*189); c.803+1G&gt;C (splice site mutation) in Patients 1\u20132; c.638dupA (p.Val214Glyfs*189); c.419T&gt;C (p.Leu140Pro) in Patient 3; and c.171delG (p.Glu57Aspfs*7); c.419T&gt;C (p.Leu140Pro) in Patient 4. Only the c.638dupA (p.Val214Glyfs*189) mutation has been previously reported in association with RMFSL. These patients illustrate that, compared with RMFSL, <jats:italic>BRAT1<\/jats:italic> mutations can result in both moderately severe presentations evident by later\u2010onset epilepsy and survival past infancy, as well as milder presentations that include intellectual disability, ataxia\/dyspraxia, and cerebellar atrophy. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37783","type":"journal-article","created":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T03:23:15Z","timestamp":1465528995000},"page":"2265-2273","source":"Crossref","is-referenced-by-count":48,"title":["<i>BRAT1<\/i> mutations present with a spectrum of clinical severity"],"prefix":"10.1002","volume":"170","author":[{"given":"Siddharth","family":"Srivastava","sequence":"first","affiliation":[{"name":"Hugo W. Moser Research Institute at Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Neurology The Johns Hopkins Hospital Baltimore Maryland"},{"name":"Department of Pediatrics The Johns Hopkins Hospital Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather E.","family":"Olson","sequence":"additional","affiliation":[{"name":"Epilepsy Genetics Program Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Hugo W. 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