SLC5A7 encodes the presynaptic sodium-dependant high-affinity choline transporter 1 (CHT), which uptakes choline to the presynaptic nerve terminal following the breakdown of acetylcholine by the acetylcholinesterase within the synaptic cleft. We report 5 patients from three consanguineous families with congenital myasthenic syndrome type 20 caused by novel mutations in SLC5A7. The individuals from family 1 and 2 were homozygous for c.320G>A; (p.Arg107His) and c.886G>A (p.Ala296Thr), respectively, and their phenotype was characterised by recurrent apnoeic attacks early after birth and learning and speech difficulties in childhood. Individuals from family 3 were homozygous for c.1240T>A (p.Tyr414Asn) and suffered from more severe central and peripheral manifestations with lack of spontaneous movements and respiratory drive and overall minimal response to external stimuli. All individuals tested showed neurophysiological defects compatible with impaired neuromuscular transmission. Combined treatment with cholinesterase inhibitors and β2-adrenergic agonists was beneficial in patients from family 1 and 2. Affected individuals from family 3 died from complications directly related to their underlying genetic condition. This report provides three novel pathogenic variants in SLC5A7 and highlights the variability in the clinical phenotype, severity and prognosis of this syndrome.

中文翻译：

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由编码钠依赖性高亲和力胆碱转运蛋白的 SLC5A7 中的三个新突变引起的突触前先天性肌无力综合征

SLC5A7 编码突触前钠依赖性高亲和力胆碱转运蛋白 1 (CHT)，它在突触间隙内的乙酰胆碱酯酶分解乙酰胆碱后将胆碱摄取到突触前神经末梢。我们报告了来自三个近亲家庭的 5 名患者，这些患者患有由 SLC5A7 中的新突变引起的先天性肌无力综合征 20 型。家族 1 和家族 2 的个体为 c.320G>A 纯合子；(p.Arg107His) 和 c.886G>A (p.Ala296Thr)，其表型的特点是出生后早期呼吸暂停反复发作以及儿童时期的学习和言语困难。来自家族 3 的个体对于 c.1240T>A 是纯合子 (p. Tyr414Asn) 并患有更严重的中枢和外周表现，缺乏自发运动和呼吸驱动，对外部刺激的总体反应很小。所有接受测试的人都表现出与神经肌肉传递受损相容的神经生理缺陷。胆碱酯酶抑制剂和 β2-肾上腺素能激动剂的联合治疗对家族 1 和家族 2 的患者有益。家族 3 的受影响个体死于与其潜在遗传状况直接相关的并发症。该报告提供了 SLC5A7 中的三个新的致病变异，并强调了该综合征临床表型、严重程度和预后的变异性。胆碱酯酶抑制剂和 β2-肾上腺素能激动剂的联合治疗对家族 1 和家族 2 的患者有益。家族 3 的受影响个体死于与其潜在遗传状况直接相关的并发症。该报告提供了 SLC5A7 中的三个新的致病变异，并强调了该综合征的临床表型、严重程度和预后的变异性。胆碱酯酶抑制剂和 β2-肾上腺素能激动剂的联合治疗对家族 1 和家族 2 的患者有益。家族 3 的受影响个体死于与其潜在遗传状况直接相关的并发症。该报告提供了 SLC5A7 中的三个新的致病变异，并强调了该综合征临床表型、严重程度和预后的变异性。