AUTHOR=An Ran , Chen Huijiao , Lei Song , Li Yi , Xu Yanming , He Chengqi 

TITLE=Abnormal decrement on high-frequency repetitive nerve stimulation in congenital myasthenic syndrome with GFPT1 mutations and review of literature

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.926786

DOI=10.3389/fneur.2022.926786

ISSN=1664-2295

ABSTRACT=Objectives: Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders characterized by neuromuscular junction defects. Mutations in GFPT1 have been shown to underlie CMS. An increasing number of patients with CMS due to mutations in GFPT1 have been reported. However, a comprehensive review of clinical and genetic analyses of GFPT-related CMS from worldwide are lacking, especially common or hotspot mutations in in GFPT1 have not been reported. Here, we described the clinical and genetic findings of three patients with GFPT1 mutations from southwestern China and reviewed the clinical and genetic features of GFPT1-related CMS patients worldwide.
Methods: Clinical, laboratory, electrophysiological, myopathological and genetic analyses of three patients with GFPT1-related CMS from southwestern China were conducted and review of previously published or reported cases about congenital myasthenic syndrome with GFPT1 mutations in PubMed database was made.
Results: The clinical, laboratory, electrophysiological, and myopathological features by muscle biopsy of three patients with GFPT1-related CMS were consistent with those of previously reported patients with GFPT1 mutations. Additionally, an abnormal decrement on high-frequency RNS was found. Two different homozygous missense mutations (c.331C>T, p.R111C; c.44C>T, p.T15M) were detected by whole-exome sequencing or targeted neuromuscular disorder gene panels. 
Conclusion: A distinct decremental response on high-frequency RNS was found in three GFPT1-related CMS patients from southwestern China, which have never been reported thus far. In addition, the location and degree of tubular aggregates seemed to be associated with the severity of clinical symptoms and serum creatine kinase levels, further expanding the phenotypic spectrum of GFPT1-related CMS. Lastly, some potential hotspot mutations in GFPT1 have been found in GFPT1-CMS worldwide.