{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:09:53Z","timestamp":1791317393239,"version":"4.3.1"},"reference-count":11,"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"}],"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>We describe two siblings who were affected with early onset focal seizures, severe progressive postnatal microcephaly, muscular hypertonia, feeding problems and bouts of apnea, only minimal psychomotor development, as well as death in infancy and childhood. We identified compound heterozygous mutations in <jats:italic>BRAT1<\/jats:italic> exons 5 (c.638_639insA) and 8 (c.1134+1G&gt;A) in one affected child via next\u2010generation sequencing of the disease\u2010associated genome followed by phenotype\u2010driven bioinformatic analysis. Sanger sequencing confirmed the presence of these mutations in both patients and a heterozygote status of the parents. Whereas the frameshift mutation (c.638_639insA) has been described in one family, the splice\u2010site mutation (c.1134+1G&gt;A) is novel. In contrast to all cases published so far, one of our patients showed a considerably milder clinical course with survival into childhood. Investigation of a skeletal muscle biopsy showed a severely reduced COX enzyme histochemical staining, indicating mitochondrial dysfunction. Our data expand the clinical and mutational spectrum of the <jats:italic>BRAT1<\/jats:italic>\u2010associated phenotype. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37798","type":"journal-article","created":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T03:23:06Z","timestamp":1465528986000},"page":"2274-2281","source":"Crossref","is-referenced-by-count":28,"title":["<i>BRAT1<\/i> mutations are associated with infantile epileptic encephalopathy, mitochondrial dysfunction, and survival into childhood"],"prefix":"10.1002","volume":"170","author":[{"given":"Denise","family":"Horn","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik und Humangenetik Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Weschke","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr P\u00e4diatrie m.S. Neurologie &amp; NeuroCure Clinical Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Knierim","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr P\u00e4diatrie m.S. Neurologie &amp; NeuroCure Clinical Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Fischer\u2010Zirnsak","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik und Humangenetik Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max\u2010Planck\u2010Institut f\u00fcr Molekulare Genetik FG Development &amp; Disease Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Stenzel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Neuropathologie Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr P\u00e4diatrie m.S. Neurologie &amp; NeuroCure Clinical Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Zemojtel","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry Polish Academy of Sciences Poznan Poland"},{"name":"Labor Berlin\u2013Charit\u00e9 Vivantes GmbH Humangenetik Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510332200"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2015.09.002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ajmg.a.37434","article-title":"BRAT1\u2010related disease\u2010identification of a patient without early lethality","volume":"170","author":"Mundy SA","year":"2015","journal-title":"Am J Med Genet Part A"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028936"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.91"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004041"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440420"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-548"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2014.11.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01877.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009262"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37798","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:39:46Z","timestamp":1696635586000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,9]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/ajmg.a.37798"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37798","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,9]]}}}