Tehran University of Medical Sciences

Science Communicator Platform

Share By
A Cohort of Iranian Patients With Congenital Myasthenic Syndrome Due to Glycosylation Defects Publisher Pubmed



Ramezani M ; Okhovat AA ; Nilipour Y ; Ghasemi A ; Ashtiani BH ; Sarraf P ; Kariminejad A ; Nafissi S
Authors

Source: Muscle and Nerve Published:2026


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. © 2025 Wiley Periodicals LLC.
Related Docs
View other Related Docs
1. Late-Onset Pompe Disease in Iran: A Clinical and Genetic Report, Muscle and Nerve (2017)
2. Intrafamilial Phenotypic Variability Due to a Missense Pathogenic Variant in Fbp1 Gene, Molecular Genetics and Metabolism Reports (2024)
3. Genetics of Gne Myopathy in the Non-Jewish Persian Population, European Journal of Human Genetics (2016)
Experts (# of related papers)
View all Related Experts
Mahmoudreza Ashrafi (4)
Reza Shervin Badv (3)
Other Related Docs
4. Three Novel Variants Identified in Fbn1 and Tgfbr2 in Seven Iranian Families With Suspected Marfan Syndrome, Molecular Genetics and Genomic Medicine (2020)
5. Gdap1-Related Charcot–Marie–Tooth Disease: Axonal or Demyelinating Subtype? Autosomal Recessive or Autosomal Dominant Inheritance?, Journal of the Peripheral Nervous System (2025)
6. Colq-Related Congenital Myasthenic Syndrome: An Integrative View, Neurogenetics (2023)
7. A Case Report of Congenital Myasthenic Syndrome Caused by a Mutation in the Chrne Gene in the Iranian Population, Iranian Journal of Child Neurology (2020)
8. High Occurrence of a Missense Variant (C.471C>A) in the Fgf23 Gene Related to Hyperostosis–Hyperphosphatemia Syndrome With a Possible Founder Effect, Human Mutation (2025)
9. Genetic and Clinical Insights Into Pontocerebellar Hypoplasia: Identification of Novel Variants in an Iranian Cohort, European Journal of Medical Genetics (2026)
10. Causative Variants Linked With Limb Girdle Muscular Dystrophy in an Iranian Population: 6 Novel Variants, Molecular Genetics and Genomic Medicine (2023)
11. Molecular Genetic Study of Glutaric Aciduria, Type I: Identification of a Novel Mutation, Journal of Cellular Biochemistry (2019)
12. Genetic Homogeneity of a Tdp1 Variant, C.1478A>G, As the Main Disease-Causing Variant of Spinocerebellar Ataxia With Axonal Neuropathy 1 (Scan1) in the Middle East: A Systematic Review, Pediatric Neurology (2025)
13. Tpp1 Variants in Iranian Patients: A Novel Pathogenic Homozygous Variant Causing Neuronal Ceroid Lipofuscinosis 2, Molecular Syndromology (2024)
14. Phenotype and Genotype Correlation in Iranian Primary Congenital Glaucoma Patients, Journal of Glaucoma (2016)
15. Identifying Novel Agrn Variants in Congenital Myasthenic Syndrome: Insights From Three Iranian Families, Neuromuscular Disorders (2025)
16. Ngly1 Deficiency: Novel Variants and Literature Review, European Journal of Medical Genetics (2021)
17. Clinical and Genetic Diversity in Iranian Individuals With Rapsn-Related Congenital Myasthenic Syndrome, Neurogenetics (2025)
18. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
19. A Comprehensive Study of Mutation and Phenotypic Heterogeneity of Childhood Mitochondrial Leukodystrophies, Brain and Development (2024)
20. Sequential Targeted Exome Sequencing of 1001 Patients Affected by Unexplained Limb-Girdle Weakness, Genetics in Medicine (2020)