A case of severe spinal muscular atrophy type 1 resistant to specific treatment due to a missense variant in the Tudor domain of SMN1

Tsuyoshi Aihara , Yuichi Abe , Atsushi Nishioka , Itaru Hayakawa
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Abstract

Introduction

Spinal muscular atrophy (SMA) is a genetic disorder characterized by muscle weakness and atrophy due to degeneration of anterior horn cells in the spinal cord. It typically results from the allele deletion of SMN1 alleles (null-SMN1). With the implementation of newborn screening for SMA (SMA-NBS), most null-SMN1 patients are diagnosed in a presymptomatic stage.

Case report

A full-term male infant initially had a negative SMA-NBS result but presented with muscle weakness within his first month. By two months, genetic testing identified a single allele deletion and a point variant in the Tudor domain of SMN1, along with three copies of SMN2, confirming SMA type I. The patient was treated with onasemnogene abeparvovec (OA) gene therapy. However, despite the presence of three SMN2 copies and OA treatment, he eventually required respiratory support, including tracheostomy and mechanical ventilation. At one year and seven months, risdiplam therapy was initiated.

Conclusion

SMA patients with SMN1 variants may bypass SMA-NBS and can develop severe SMA, depending on variant type, regardless of SMN2 copy number.
由于SMN1都铎结构域的错义变异,1型严重脊髓性肌萎缩症对特异性治疗产生抗性
脊髓性肌萎缩症(SMA)是一种遗传性疾病,以脊髓前角细胞变性引起的肌肉无力和萎缩为特征。它通常是由SMN1等位基因缺失(null-SMN1)引起的。随着新生儿SMA筛查(SMA- nbs)的实施,大多数无smn1患者在症状前阶段被诊断出来。病例报告1例足月男婴最初有阴性SMA-NBS结果,但在第一个月内出现肌肉无力。两个月后,基因检测发现SMN1 Tudor结构域的单个等位基因缺失和一个点变异,以及SMN2的三个拷贝,确认为SMA i型。患者接受onasemnogene abeparvovec (OA)基因治疗。然而,尽管存在3个SMN2拷贝和OA治疗,他最终需要呼吸支持,包括气管造口术和机械通气。在1岁零7个月时,开始了瑞斯迪普兰治疗。结论SMN1变异的SMA患者可能会绕过SMA- nbs,并可能发展为严重的SMA,这取决于变异类型,与SMN2拷贝数无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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