Abstract：
Spinal Muscular Atrophy (SMA) emerges as a prominent genetic neuromuscular disorder primarily caused by variants in the survival motor neuron (SMN) gene. However, it is noteworthy that alternative variants impacting DYNC1H1 have also been linked to a subtype known as spinal muscular atrophy lower extremity predominant (SMA-LED). This observation underscores the complexity of SMA and highlights the necessity for tailored, gene-specific management strategies. Our study elucidates how similar approaches to managing SMA can yield distinct outcomes, emphasizing the imperative for personalized gene-based interventions in effectively addressing these conditions. Two patients were referred for further management due to clinical suspicion of type-3 SMA. The definitive diagnosis was confirmed through the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique, as well as whole-exome sequencing (WES). The analysis revealed deletions in exon-7 and 8 of SMN1 in the first patient and a likely pathogenic mutation (NM_001376.5(DYNC1H1):c.1867 T > C (NP_001367.2: p.Phe623Leu)) in DYNC1H1 in the second patient. Both patients presented with lower limb muscle weakness. However, while the first patient exhibited a gradual increase in severity over the years, the second patient displayed no progressive symptoms. The management was adjusted accordingly based on the genetic findings. Our observation underscores the complexity of SMA and highlights the necessity for tailored, gene-specific management strategies. Our study elucidates how similar approaches to managing SMA can yield distinct outcomes, emphasizing the imperative for personalized gene-based interventions in effectively addressing these conditions.
摘要：
脊髓性肌萎缩症（SMA）是一种主要由存活运动神经元（SMN）基因变异引起的突出的遗传性神经肌肉疾病。然而,值得注意的是,影响DYNC1H1的替代变异体也与一种称为脊髓性肌萎缩症(SMA-LED)的亚型相关.这一观察强调了SMA的复杂性，并强调了定制的必要性，基因特异性管理策略。我们的研究阐明了管理SMA的类似方法如何产生不同的结果，强调个性化的基于基因的干预措施在有效解决这些条件的必要性。由于临床怀疑3型SMA，两名患者被转诊接受进一步治疗。通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）技术证实了明确的诊断，以及全外显子组测序（WES）。分析显示，第一例患者的SMN1外显子7和8缺失，第二例患者的DYNC1H1可能有致病性突变（NM_001376.5（DYNC1H1）：c.1867T>C（NP_001367.2：p.Phe623Leu））。两名患者均表现为下肢肌肉无力。然而,虽然第一位患者多年来表现出严重程度的逐渐增加，第二名患者没有出现进行性症状.根据遗传发现相应地调整管理。我们的观察强调了SMA的复杂性，并强调了定制的必要性，基因特异性管理策略。我们的研究阐明了管理SMA的类似方法如何产生不同的结果，强调个性化的基于基因的干预措施在有效解决这些条件的必要性。
