Muscle Nerve. 2025 Nov 28. doi: 10.1002/mus.70083. Online ahead of print.
ABSTRACT
INTRODUCTION/AIMS: Glycosylation defects are a recognized cause of congenital myasthenic syndrome (CMS), affecting the stability and functions of the neuromuscular junction proteins. Mutations in five genes (GFPT1, DPAGT1, GMPPB, ALG2, and ALG14) are currently associated with glycosylation-related CMS. This cohort describes Iranian patients with CMS and variants in these genes.
METHODS: A retrospective study was conducted to examine demographic, clinical, genetic, and histological data from Iranian patients with confirmed CMS-glycosylation defects. Patients were identified and recruited through the Neuromuscular Clinics of Tehran University of Medical Sciences. Only patients with complete clinical and genetic data available were included.
RESULTS: Twenty-three genetically confirmed patients with glycosylation-related CMS were enrolled. Genetic analysis revealed the mutations in the GFPT1, GMPPB, and ALG2 genes, with those in GFPT1 and GMPPB being the most common. The median age of onset and diagnosis was 6 and 16 years, respectively. Common clinical features were limb-girdle muscle weakness with minimal ocular involvement. Consanguinity and a positive family history were common, identified in 21 and 14 patients, respectively. Muscle biopsies revealed tubular aggregates in patients with GFPT1 and GMPPB variants. In addition, novel genetic variants were identified, and phenotypic variability was observed even within families sharing identical mutations.
DISCUSSION: This study identifies novel variants and phenotypic variability in glycosylation-related CMS, with GFPT1 and GMPPB as the predominant subtypes in Iran. These findings expand the genotypic and phenotypic spectrum and underscore the importance of early genetic testing in high-consanguinity populations to improve diagnosis and management.
PMID:41312578 | DOI:10.1002/mus.70083
