Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.
Intern Med. 2022 Mar 15;61(6):887-890. doi: 10.2169/internalmedicine.7774-21. Epub 2021 Aug 24.
The patient had suffered from both proximal and distal limb weakness since her early childhood, without the involvement of ocular or respiratory muscles. Repetitive nerve stimulation (RNS) at 3 Hz showed significant decrement in the area and amplitude of the compound muscle action potential (CMAP) on the right abductor digiti minimi (26%) and trapezius (17%). Whole-exon sequencing revealed two novel heterozygous mutations (p.Q1406Rfs*29 and p.R1521H) in the LG1 domain of agrin, which were deemed likely pathogenic for congenital myasthenic syndromes (CMS) according to a bioinformatics analysis. The patient showed remarkable improvement after treatment with salbutamol. This case expanded the mutation spectrum of AGRN.
患者自幼年起即出现四肢近端和远端肌无力，眼肌和呼吸肌不受累。右侧小指展肌（26%）和斜方肌（17%）的复合肌肉动作电位（CMAP）的面积和幅度在 3Hz 重复神经刺激（RNS）时出现明显递减。外显子组测序显示 agrin 的 LG1 结构域中存在两个新的杂合突变（p.Q1406Rfs*29 和 p.R1521H），根据生物信息学分析，这两个突变被认为可能与先天性肌无力综合征（CMS）相关。患者使用沙丁胺醇治疗后症状显著改善。该病例扩展了 AGRN 的突变谱。
