{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified that intronic repeat expansions in SAMD12, primarily of TTTCA and TTTTA motifs within intron 4, play a crucial role in the pathogenesis of familial myoclonic epilepsies. Multiple independent investigations across diverse populations—including Japanese, Chinese, Thai, Indian, and Sri Lankan cohorts—demonstrated that these noncoding repeat expansions in SAMD12 (as well as in related genes) are consistently associated with the onset of benign adult familial myoclonic epilepsy (BAFME) and familial cortical myoclonic tremor with epilepsy (FCMTE). These findings underscore how unstable intronic repeats in SAMD12 act as a genetic trigger, leading to neuronal dysfunction and the characteristic clinical features of myoclonic tremor and epilepsy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a distinct context, the SAMD12 locus also gives rise to a long non‐coding RNA—SAMD12‑AS1—that is upregulated in conditions such as hepatitis B virus infection and glioma, thereby contributing to oncogenesis. Functional studies revealed that elevated SAMD12‑AS1 promotes cell proliferation and impairs apoptosis by interacting with proteins such as NPM1 and HDM2, which in turn facilitate enhanced degradation of p53. In parallel, reduced levels of SAMD12 have been linked with increased proliferative capacity in liver cancer models, suggesting that the SAMD12 locus is involved in both neurological disorders via repeat expansions and in tumorigenesis through regulatory RNA mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroyuki Ishiura, Koichiro Doi, Jun Mitsui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-018-0067-2"}], "href": "https://doi.org/10.1038/s41588-018-0067-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29507423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29507423"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sheng Zeng, Mei-Yun Zhang, Xue-Jing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long-read sequencing identified intronic repeat expansions in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SAMD12"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " from Chinese pedigrees affected with familial cortical myoclonic tremor with epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2018-105484"}], "href": "https://doi.org/10.1136/jmedgenet-2018-105484"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30194086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30194086"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhidong Cen, You Chen, Dehao Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intronic (TTTGA)"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "n"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " insertion in SAMD12 also causes familial cortical myoclonic tremor with epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mov Disord (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mds.27832"}], "href": "https://doi.org/10.1002/mds.27832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31483537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31483537"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mark F Bennett, Karen L Oliver, Brigid M Regan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-020-0606-z"}], "href": "https://doi.org/10.1038/s41431-020-0606-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32203200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32203200"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Patra Yeetong, Chaipat Chunharas, Monnat Pongpanich, et al. 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