Lei Lijing, Peng Linliu, Wan Linlin, Chen Zhao, Wang Chunrong, Peng Huirong, Qiu Rong, Tang Beisha, Jiang Hong
Department of Neurology, Xiangya Hospital, Central South University, Changsha, P. R. China.
Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, P. R. China.
Mov Disord. 2025 Feb;40(2):324-334. doi: 10.1002/mds.30083. Epub 2024 Dec 19.
Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.
The aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying causal factors, healthy controls for determining the normal range, and ATX-ATXN3 (spinocerebellar ataxia type 3, SCA3) patients for exploring genetic modifiers.
We combined whole-genome sequencing (WGS), repeat-primed polymerase chain reaction, capillary electrophoresis (RP-PCR/CE), and ExpansionHunter to screen the GCA repeats in the GLS gene of 349 undiagnosed ataxia individuals, 1505 healthy controls, and 1236 ATX-ATXN3 (SCA3) patients from mainland China.
No expanded GCA repeats in the GLS gene were detected across any of the samples. The average number of GCA repeats was 11 (range: 8-31), 12 (range: 6-33), and 11 (range: 6-33) for undiagnosed ataxia patients, healthy controls, and SCA3 patients, respectively. The intermediate repeat size (9 < repeat size ≤ 13) of the nonexpanded GCA allele in the GLS gene was associated with later disease onset in ATX-ATXN3 (SCA3) patients.
Abnormal expansions of GLS GCA repeats are rare in the Chinese population. However, intermediate-length normal GCA repeat sizes may influence the age at onset (AAO) in ATX-ATXN3 (SCA3) patients. © 2024 International Parkinson and Movement Disorder Society.
最近的研究报告称，GLS基因中扩展的GCA重复序列可导致伴有共济失调表型的谷氨酰胺酶缺乏症。然而，截至目前，尚无研究调查中国人群中GLS基因GCA重复序列的分布及作用。
旨在调查中国人群中GCA重复序列的分布情况，包括未确诊的共济失调患者以确定致病因素、健康对照以确定正常范围，以及脊髓小脑共济失调3型（SCA3）患者以探索基因修饰因子。
我们结合全基因组测序（WGS）、重复引物聚合酶链反应、毛细管电泳（RP-PCR/CE）和ExpansionHunter，对来自中国大陆的349例未确诊的共济失调个体、1505例健康对照和1236例SCA3患者的GLS基因中的GCA重复序列进行筛选。
在所有样本中均未检测到GLS基因中扩展的GCA重复序列。未确诊的共济失调患者、健康对照和SCA3患者的GCA重复序列平均数分别为11（范围：8 - 31）、12（范围：6 - 33）和11（范围：6 - 33）。GLS基因中未扩展的GCA等位基因的中等重复长度（9＜重复长度≤13）与SCA3患者较晚的疾病发病相关。
GLS基因GCA重复序列的异常扩展在中国人群中较为罕见。然而，中等长度的正常GCA重复长度可能会影响SCA3患者的发病年龄（AAO）。© 2024国际帕金森和运动障碍协会。
