摘要目的:探讨运动神经元存活基因2( SMN2)拷贝数及 SMN2全长转录本( fl-SMN2)水平在脊髓性肌萎缩症(SMA)1－3型患儿中的分布，明确其对疾病表型、进展及预后评估的意义及影响。 方法:回顾性分析2019年1月至2021年12月到首都儿科研究所就诊并经基因诊断为 SMN1纯合缺失且未经治疗的78例SMA患儿的临床资料，采集患儿的临床横断面数据，包括发病年龄、获得的运动功能、并发症等，并随访采集运动功能退化及生存数据，同时测定患儿携带的 SMN2拷贝数和 fl-SMN2转录水平，应用 t检验或单因素方差分析或 χ2检验进行组间比较，Kaplan－Meier分析用于生存分析， Kendall′ s tau- c分析这两个标志物与疾病表型、发病年龄、运动进展及结局之间的相关性。 结果:78例SMA患儿中1型为17例(21.8%)，2型34例(43.6%)，3型27例(34.6%)。约41.2%(7/17)的1型患儿死亡，中位生存年龄为11个月，2型和3型患儿中未观察到死亡。携带2、3和4个 SMN2拷贝患儿的中位发病年龄分别为1.8、12.0和24.0个月( F＝4.943， P＝0.01)， fl-SMN2转录水平均值分别为196.25±68.79、331.21±108.79和455.69±122.27( F＝37.154， P<0.001)。2拷贝 SMN2的患儿1年、2年和5年时的生存率分别为50.5%、0、0，中位生存期为7个月，而在3拷贝和4拷贝的5年生存率分别为97.4%和100.0%。 fl-SMN2转录水平与SMA表型严重程度呈负相关( Kendall′ s tau- c＝－0.444， P<0.001)，且存活患儿的 fl-SMN2转录水平(342.93±125.74)明显高于死亡患儿的水平(212.14±92.31)。在运动功能的获得方面均表现出 SMN2拷贝数越多， fl-SMN2转录水平越高，获得的运动功能也越多的趋势( P<0.001)。此外， fl-SMN2转录水平在独坐和独站功能未退化组和功能退化组差异有统计学意义( F＝5.432， P＝0.023； F＝4.315， P＝0.047)。 结论:SMN2拷贝数和 fl-SMN2转录水平均与SMA表型严重程度和生存状况有关，是评估SMA表型重要的生物标志物。 fl-SMN2转录水平还可能与独坐和独站功能的退化相关。

abstractsObjective:To explore the distribution of the copy number of survival motor neuron gene 2 ( SMN2) and the transcript level of the full-length SMN2 ( fl-SMN2) transcript level in patients with type 1-3 spinal muscular atrophy (SMA), and to evaluate their influences on disease severity, progression, and prognosis. Methods:It was a retrospective study involving 78 therapy-naive SMA patients with SMN1 gene homozygous deletion who were diagnosed and treated in the Capital Institute of Pediatrics from January 2019 to December 2021.Cross-sectional clinical data, including age at onset, motor milestones, and complications were recorded.They were followed up for monitoring motor function degeneration and survival.The copy number of SMN2 and the transcript level of fl-SMN2 were detected.Differences between groups were compared by the Student′s t-test or One- Way ANOVA or Chi- square test.Kaplan-Meier analysis was used for survival analysis, and Kendall′ s tau- c was performed to assess the correlation of these two biomarkers with SMA phenotypes, age at onset, motor milestones, and survival. Results:Of the 78 SMA patients, there were 17 cases (21.8%) of type 1, 34 cases(43.6%) of type 2, and 27 cases(34.6%) of type 3.Seven cases(41.2%) type 1 SMA patients died, with a median survival time of 11 months, and no deaths were observed in type 2 and type 3 SMA patients.There was a significant difference in the median age at onset among SMA patients with 2, 3, and 4 copies of SMN2 (1.8, 12.0, and 24.0 months, respectively; F=4.943, P=0.01). The mean transcript level of fl-SMN2 in type 1, 2 and 3 SMA patients were 196.25±68.79, 331.21±108.79 and 455.69±122.27, respectively ( F=37.154, P<0.001). The survival rate of SMA with 2 SMN2 copies at 1, 2, and 5 years were 50.5%, 0, and 0, respectively, and their median survival age was 7 months.The survival rate of SMA with 3 and 4 SMN2 copies at 5 years were 97.4% and 100.0%, respectively.Moreover, a negative correlation was observed between the transcript level of fl-SMN2 and phenotype severity ( Kendall′ s tau- c=-0.444, P<0.001), and the transcript level of fl-SMN2 of the survival group was much higher than that of the death group (342.93±125.74 vs.212.14±92.31). More copies of SMN2 and higher transcript level of fl- SMN2 indicated more motor function acquisitions (head control, sitting and walking) ( P<0.001). In addition, there was a significant difference in the transcription level of fl-SMN2 between the undegenerated group and the degenerated group in sitting and standing ( F=5.432, P=0.023 and F=4.315, P=0.047, respectively). Conclusions:Both the copy number of SMN2 and the transcript level of fl-SMN2 are correlated with SMA severity, survival, and motor milestones, serving as valuable biomarkers for evaluating phenotypic severity of SMA.The transcript level of fl-SMN2 s may play an important role in the degeneration of sitting and standing.