Abstract
Congenital myasthenic syndrome (CMS) constitutes a group of inherited disorders of neuromuscular junctions. The majority of postsynaptic syndromes result from mutations in the CHRNE gene that causes muscle nicotine acetylcholine deficiency. In this study, we report on a 2 and a half-year-old boy with normal developmental milestones and bilateral ptosis. Clinical courses, electrophysiological studies and molecular genetic analysis were assessed. Polymerase chain reaction (PCR) and direct DNA sequencing of the CHRNE gene were performed for the proband and all the family members. A novel homozygous missense mutation of c.973G>T was found in the CHRNE gene. Segregation studies were suggested to be the genetic cause of the disease. Using three in silico tools and the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant classification guidelines indicated that the novel variant c.973G>T was likely pathogenic. Our results recommended first screening of the CHRNE gene for pathogenic mutations in Iranian origin.