Novel LG1 Mutations in Agrin Causing Congenital Myasthenia Syndrome.

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.