目的 总结2例运动神经元存活基因1（SMN1）外显子1结构变异致脊髓性肌萎缩症（SMA）的临床表型和基因型特点。方法 回顾性分析2022年10月至2024年6月在神经内科就诊的2例外显子1结构变异致SMA患儿的临床资料，采集患儿及父母的外周血样，最终经长片段PCR技术结合多重连接探针扩增技术（MLPA）-P021明确5qSMA诊断，并对SMN1基因外显子1变异致SMA相关文献进行总结分析。结果 2例外显子1结构变异致SMA患儿均为男性，Ⅱ型，发病年龄分别为7月龄及9月龄，就诊年龄分别为9岁1月龄及1岁1月龄，均表现为四肢肌无力和运动发育落后，肌电图均提示脊髓前角病变。2例患儿常规MLPA检测均为SMN1基因杂合缺失，最终经长片段PCR结合MLPA-P021确诊，检测结果均显示SMN1基因外显子7拷贝数为1，同时该等位基因上检测到外显子1结构缺失变异。此外，例1患儿的该等位基因可能为SMN1/SMN2转换基因。例1患儿出生时间较早且其基因转换并结构变异较为罕见，诊断时间窗长达11年。文献检索共纳入7篇外显子1变异致SMA相关文献，包括错义变异、无义变异及结构缺失变异等，共19例，男女比12∶7。患者在出生到青春期不同年龄起病，主要表现为运动功能落后或退步，其中5例已宣告死亡，部分接受SMA精准治疗的患者情况尚可。结论 该研究2例SMA患儿均为SMN1基因外显子1结构变异所致5qSMA。当临床疑似SMA患者初次MLPA检测为阴性即外显子7未出现纯合缺失时，需考虑到SMN1基因外显子1变异，通过优化的长片段PCR结合MLPA-P021技术可快速精准明确诊断。外显子1可能为中国SMA变异图谱热点，同时基因转换值得关注。

Objective To report and analyze the clinical phenotypes and genotypes of two cases of spinal muscular atrophy (SMA) caused by structural variations in exon 1 of the survival motor neuron 1 (SMN1) gene. Methods A retrospective analysis was conducted on the clinical data of two children with SMA caused by structural variations in exon 1 who visited the neurology department from October 2022 to June 2024. Peripheral blood samples were collected from the patients and their parents. Diagnosis of 5q SMA was ultimately confirmed using long-range PCR (LR-PCR) combined with multiplex ligation-dependent probe amplification (MLPA) kit P021. A literature review of SMA cases associated with exon 1 variations in SMN1 gene was also conducted. Results Both of the two children with SMA caused by structural variations in exon 1 were male, type Ⅱ. Their ages of onset were 7 months and 9 months respectively, and their ages of seeking medical attention were 9 years and 1 month and 1 year and 1 month respectively. They all presented with limb muscle weakness and delayed motor development, and electromyography all indicated lesions in the anterior horn of the spinal cord. Routine MLPA testing initially identified heterozygous deletion of the SMN1 gene in both patients. Definitive diagnosis via LR-PCR combined with MLPA-P021 revealed an SMN1 exon 7 copy number of 1 on one allele, coupled with a structural deletion variant in exon 1 on the same allele. Additionally, Patient 1 harbored an SMN1/SMN2 hybrid gene on this allele. The extended diagnostic interval of 11 years for Patient 1 was attributed to both the earlier time of birth and the rarity of the combined gene conversion and structural variation. Literature review identified 7 relevant publications reporting 19 SMA cases (male-to-female ratio 12∶7) caused by exon 1 variations, including missense, nonsense, and structural deletion variants. Age of onset ranged from birth to adolescence, with primary manifestations being motor function delay or regression. Five patients were deceased; some receiving SMA-targeted therapies were reported to be stable. Conclusions Both SMA cases in this study were caused by structural variations in exon 1 of the SMN1 gene, confirming 5q SMA. When initial MLPA testing in clinically suspected SMA patients is negative (i.e., no homozygous deletion of exon 7 is detected), variations in exon 1 should be considered. The optimized LR-PCR combined with MLPA-P021 technique enables rapid and precise diagnosis. Exon 1 may represent a hotspot in the Chinese SMA variant spectrum, and gene conversion events warrant particular attention.