Morikawa Takuya, Miura Shiroh, Fan Luoming, Watanabe Emina, Fujioka Ryuta, Motooka Hiromichi, Yasumoto Shingo, Uchiyama Yusuke, Shibata Hiroki
Division of Genomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, 454, Shitsukawa, Toon, Ehime, Japan.
Hum Genome Var. 2022 Aug 22;9(1):29. doi: 10.1038/s41439-022-00207-8.
Dystonia (DYT) is a heterogeneous neurological disorder, and there are many types of DYT depending on the responsible genes. DYT11 is an autosomal dominant DYT caused by functional variants in the SGCE gene. We examined a Japanese patient with myoclonic dystonia. By using exome analysis, we identified a rare variant in the SGCE gene, NM_003919.3: c.304C > T [Arg102*], in this patient. Therefore, this patient has been molecularly diagnosed with DYT11. By Sanger sequencing, we confirmed that this variant was paternally inherited in this patient. By allele-specific PCR, we confirmed that the maternally inherited normal allele of SGCE was silenced, and only the paternally inherited variant allele was expressed in this patient. Despite the pathogenicity, identical variants have been recurrently reported in eight independent families from different ethnicities, suggesting recurrent mutations at this mutational hotspot in SGCE.
肌张力障碍（DYT）是一种异质性神经疾病，根据致病基因的不同，有多种类型的DYT。DYT11是由SGCE基因功能变异引起的常染色体显性DYT。我们检查了一名患有肌阵挛性肌张力障碍的日本患者。通过外显子组分析，我们在该患者的SGCE基因（NM_003919.3）中鉴定出一个罕见变异：c.304C>T [Arg102*]。因此，该患者已被分子诊断为DYT11。通过桑格测序，我们证实该变异在该患者中是父系遗传的。通过等位基因特异性PCR，我们证实SGCE基因的母系遗传正常等位基因被沉默，且在该患者中仅父系遗传的变异等位基因表达。尽管该变异具有致病性，但在来自不同种族的八个独立家族中反复报道了相同的变异，提示SGCE基因的这个突变热点存在反复突变。
