Zhou Yuwei, Zeng Xiaofei, Zhang Luyi, Yin Xiaojie, Ma Xue, Li Keyi, Qiu Peijing, Lou Xiaoting, Jin Liqin, Wang Ya, Yang Yanling, Shen Ting
Laboratory Medicine Center, Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mol Genet Metab Rep. 2024 Dec 5;41:101168. doi: 10.1016/j.ymgmr.2024.101168. eCollection 2024 Dec.
Variants in have been reported to be associated with Leigh syndrome. However, further expansion of the -phenotype and variants spectrum of -related Leigh syndrome are still required.
Two patients diagnosed with Leigh syndrome were recruited, and whole-exome sequencing was performed to identify the genetic variants responsible for the abnormal gait, dystonia, and bilateral basal ganglia lesions, followed by validation using Sanger sequencing. Detailed medical records of the patients were collected and reviewed. Patient-derived immortalized B lymphocytes were generalized for functional assays. The clinical manifestations of the patients in this study and previously reported studies are summarized.
Two patients developed gait dystonia followed by rapid progression to generalized dystonia and psychomotor regression. Brain magnetic resonance images showed lesions in bilateral symmetric basal ganglia. We identified that patient 1 and patient 2 had two missense changes (NM_152416 c.371 T > C, c.923 T > C and c.371 T > C, c.920 A > T) in , respectively. The deficiency of mature super complex of complex I was confirmed in patient-derived immortalized B lymphocytes. Meanwhile, cellular ATP production was decreased, and mitochondrial ROS was increased. A literature review of 18 patients carrying variants in was conducted, focusing on neurological presentation.
-related Leigh syndrome is a relevant cause of initial symptoms with abnormal gait, dystonia, and bilateral basal ganglia lesions. Two novel genetic variants, c.923 T > C and c.920 A > T were reported, which expands -related Leigh syndrome and is advantageous for genetic counseling.
据报道，[基因名称]中的变异与 Leigh 综合征相关。然而，仍需要进一步扩展与[基因名称]相关的 Leigh 综合征的表型和变异谱。
招募了两名被诊断为 Leigh 综合征的患者，进行全外显子组测序以鉴定导致异常步态、肌张力障碍和双侧基底神经节病变的基因变异，随后使用 Sanger 测序进行验证。收集并回顾了患者的详细病历。对患者来源的永生化 B 淋巴细胞进行功能测定。总结了本研究及先前报道研究中患者的临床表现。
两名患者出现步态肌张力障碍，随后迅速进展为全身性肌张力障碍和精神运动发育迟缓。脑磁共振成像显示双侧对称基底神经节有病变。我们分别鉴定出患者 1 和患者 2 在[基因名称]中有两个错义变化（NM_152416 c.371 T > C、c.923 T > C 和 c.371 T > C、c.920 A > T）。在患者来源的永生化 B 淋巴细胞中证实了复合物 I 的成熟超复合物缺乏。同时，细胞 ATP 产生减少，线粒体活性氧增加。对 18 名携带[基因名称]变异的患者进行了文献综述，重点关注神经学表现。
与[基因名称]相关的 Leigh 综合征是导致异常步态、肌张力障碍和双侧基底神经节病变等初始症状的相关原因。报道了两个新的基因变异，c.923 T > C 和 c.920 A > T，这扩展了与[基因名称]相关的 Leigh 综合征，有利于遗传咨询。
