{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T03:04:49Z","timestamp":1774407889699,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat\u2010primed PCR, long\u2010range PCR, and PacBio sequencing were performed to characterize the disease\u2010causing mutation in this family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All evaluated patients manifested adult\u2010onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of <jats:italic>SAMD12<\/jats:italic> was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5\u00a0kb with 549\u2010603 copies of TTTTA and 287\u2010343 copies of TTTCA repeat motifs in this family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long\u2010range PCR products does not require high\u2010quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12450","type":"journal-article","created":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T10:03:23Z","timestamp":1606039403000},"page":"102-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and <i>SAMD12<\/i> intronic repeat expansion"],"prefix":"10.1002","volume":"6","author":[{"given":"Yongxing","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology MedStar St Mary\u2019s Hospital\/Georgetown University Hospital MedStar Medical Group Leonardtown MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raman","family":"Sood","sequence":"additional","affiliation":[{"name":"Translational and Functional Genomics Branch National Human Genome Research Institute National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Wang","sequence":"additional","affiliation":[{"name":"Epilepsy Center Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blake","family":"Carrington","sequence":"additional","affiliation":[{"name":"Translational and Functional Genomics Branch National Human Genome Research Institute National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"Park","sequence":"additional","affiliation":[{"name":"NIH Intramural Sequencing Center National Human Genome Research Institute National Institutes of Health Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice C.","family":"Young","sequence":"additional","affiliation":[{"name":"NIH Intramural Sequencing Center National Human Genome Research Institute National Institutes of Health Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"Department of Neurology Einstein Medical Center Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Children's Hospital of Illinois University of Illinois College of Medicine Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Ashizawa","sequence":"additional","affiliation":[{"name":"Houston Methodist Neurological Institute and Research Institute Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Mullikin","sequence":"additional","affiliation":[{"name":"NIH Intramural Sequencing Center National Human Genome Research Institute National Institutes of Health Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-8906","authenticated-orcid":false,"given":"Mohamad Z.","family":"Koubeissi","sequence":"additional","affiliation":[{"name":"Epilepsy Center Department of Neurology George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-025X","authenticated-orcid":false,"given":"Paul","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational and Functional Genomics Branch National Human Genome Research Institute National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.12.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.6.1180"},{"key":"e_1_2_9_4_1","first-page":"1","article-title":"Familial cortical myoclonic tremor with epilepsy and cerebellar changes: description of a new pathology case and review of the literature","volume":"2","author":"Sharifi S","year":"2012","journal-title":"Tremor Other Hyperkinet Mov (N. 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