Peng Yun, Ye Wei, Chen Zhao, Peng Huirong, Wang Puzhi, Hou Xuan, Wang Chunrong, Zhou Xin, Hou Xiaocan, Li Tianjiao, Qiu Rong, Hu Zhengmao, Tang Beisha, Jiang Hong
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
School of Information Science and Engineering, Central South University, Changsha, China.
Front Neurol. 2018 Dec 20;9:1111. doi: 10.3389/fneur.2018.01111. eCollection 2018.
Variants in have been widely reported in ataxia patients in Europe, with highly variable clinical phenotype. Until now, no mutation of ataxia has been reported among the Chinese population. Our aim was to screen for ataxia patients in China and extend the clinicogenetic spectrum. Variants in were detected by high-throughput sequencing on a cohort of 126 unrelated index patients with unexplained autosomal recessive or sporadic ataxia. Pathogenicity assessments of variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical assessments were conducted by two experienced neurologists. Two Chinese families with variable ataxia syndrome were identified (accounting for 1.6%; 2/126), separately caused by the novel homozygous mutation (NM_033071.3: c.21568C>T, p.Arg7190Ter), and compound heterozygous mutation (NM_033071.3: c.18684G>A, p.Trp6228Ter; c.17944C>T, p.Arg5982Ter), characterized by motor neuron impairment, mental retardation and arthrogryposis. ataxia exists in the Chinese population, as a rare form of autosomal recessive ataxia, with a complex phenotype. Our findings expanded the ethnic, phenotypic and genetic diversity of ataxia.
在欧洲，共济失调患者中已广泛报道了[相关基因]的变异，其临床表型高度可变。迄今为止，中国人群中尚未报道[相关基因]共济失调的突变。我们的目的是在中国筛查[相关基因]共济失调患者，并扩展临床遗传学谱。通过对126例原因不明的常染色体隐性或散发性共济失调无关索引患者队列进行高通量测序，检测[相关基因]的变异。根据美国医学遗传学与基因组学学会（ACMG）指南对[相关基因]变异进行致病性评估。通过桑格测序确认潜在的致病变异。由两名经验丰富的神经科医生进行临床评估。鉴定出两个患有可变共济失调综合征的中国家系（占1.6%；2/126），分别由新的纯合[相关基因]突变（NM_033071.3：c.21568C>T，p.Arg7190Ter）和复合杂合[相关基因]突变（NM_033071.3：c.18684G>A，p.Trp6228Ter；c.17944C>T，p.Arg5982Ter）引起，其特征为运动神经元损伤、智力障碍和关节挛缩。[相关基因]共济失调在中国人群中存在，作为一种罕见的常染色体隐性共济失调形式，具有复杂的表型。我们的发现扩展了[相关基因]共济失调的种族、表型和遗传多样性。
