Congenital myasthenic syndromes (CMS) comprise a heterogeneous group of genetic disorders of the neuromuscular junction. Next generation sequencing has been increasingly used for molecular diagnosis in CMS patients. This study aimed to identify the disease-causing variants in Thai patients. We recruited patients with a diagnosis of CMS based on clinical and electrophysiologic findings, and whole exome sequencing was performed. Thirteen patients aged from 2 to 54 years (median: 8 years) from 12 families were enrolled. Variants were identified in 9 of 13 patients (69%). Five novel variants and two previously reported variant were found in the COLQ, RAPSN and CHRND gene. The previously reported c.393+1G>A splice site variant in the COLQ gene was found in a majority of patients. Five patients harbor the homozygous splice site c.393+1G>A variant, and two patients carry compound heterozygous c.393+1G>A, c.718-1G>T, and c.393+1G>A, c.865G>T (p.Gly289Ter) variants. The novel variants were also found in RAPSN (p.Cys251del, p.Arg282Cys) and CHRND (p.Met481del). Molecular diagnosis in CMS patients can guide treatment decisions and may be life changing, especially in patients with COLQ mutations.

中文翻译：

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泰国人群先天性肌无力综合征：临床发现和新突变

先天性肌无力综合征 (CMS) 包括一组异质的神经肌肉接头遗传疾病。新一代测序已越来越多地用于 CMS 患者的分子诊断。本研究旨在确定泰国患者的致病变异。我们根据临床和电生理结果招募了诊断为 CMS 的患者，并进行了全外显子组测序。招募了来自 12 个家庭的 13 名年龄在 2 至 54 岁（中位数：8 岁）的患者。在 13 名患者中的 9 名 (69%) 中发现了变异。在 COLQ、RAPSN 和 CHRND 基因中发现了五个新变体和两个先前报道的变体。在大多数患者中发现了先前报道的 COLQ 基因中的 c.393+1G>A 剪接位点变异。五名患者携带纯合剪接位点 c.393+1G>A 变体，两名患者携带复合杂合子 c.393+1G>A、c.718-1G>T 和 c.393+1G>A、c.865G>T (p.Gly289Ter) 变体。在 RAPSN (p.Cys251del, p.Arg282Cys) 和 CHRND (p.Met481del) 中也发现了新的变体。CMS 患者的分子诊断可以指导治疗决策，并可能改变生活，尤其是在 COLQ 突变患者中。