Ma Jun, Wang Lin, Yang Yingmai, Li Shanglin, Wan Xinhua
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.
Front Neurol. 2019 Jul 4;10:729. doi: 10.3389/fneur.2019.00729. eCollection 2019.
Dystonia is a movement disorder with high clinical and genetic heterogeneity. Recently mutations in lysine-specific histone methyltransferase 2B () gene have been reported to be associated with early-onset progressive dystonia. We performed whole-exome sequencings (WES) in a cohort of early-onset dystonia patients from China. Bioinformatics analysis and cosegregation testings were conducted to select candidate causal variants. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Three novel variants were identified, including p.Q1359 in patient 1, p.R1487AfsTer7 in patient 2, and p.R152W in patient 3. Among these variants, the nonsense variant p.Q1359 and the frameshift variant p.R1487AfsTer7 showed high pathogenicity and were rated as pathogenic according to the ACMG guideline. Regarding the phenotypes of these two patients with pathogenic variants, patient 2 showed the similar presentation as reported whereas patient 1 seemly harbored the atypical presentations, including later onset age, atypical sites of onset and milder degree of dystonia. We further report three dystonia patients with novel variants in and expand the spectrums of genotype and phenotype of .
肌张力障碍是一种具有高度临床和遗传异质性的运动障碍。最近有报道称，赖氨酸特异性组蛋白甲基转移酶2B（）基因突变与早发性进行性肌张力障碍有关。我们对一组来自中国的早发性肌张力障碍患者进行了全外显子组测序（WES）。进行了生物信息学分析和共分离测试以选择候选致病变异。根据美国医学遗传学与基因组学学会（ACMG）的标准和指南对已鉴定变异的影响进行分类。鉴定出三个新变异，包括患者1中的p.Q1359、患者2中的p.R1487AfsTer7和患者3中的p.R152W。在这些变异中，无义变异p.Q1359和移码变异p.R1487AfsTer7显示出高致病性，并根据ACMG指南被评为致病。关于这两名携带致病变异患者的表型，患者2表现出与报道相似的症状，而患者1似乎具有非典型症状，包括发病年龄较晚、非典型发病部位和较轻的肌张力障碍程度。我们进一步报告了三名在中有新变异的肌张力障碍患者，并扩展了的基因型和表型谱。
