A Novel Homozygous Variant in the CHRNE Gene in 2 Siblings with Congenital Myasthenic Syndrome.

Abstract

Cholinergic receptor nicotinic epsilon (CHRNE) subunit mutations cause postsynaptic type of congenital myasthenic syndrome either as a primary acetylcholine-receptor deficiency or abnormal channel kinetics in the receptor. We report a novel homozygous variant (c.322C > T, p.Pro108Ser) in the epsilon subunit causing primary acetylcholine-receptor deficiency in two siblings. Two siblings presented with fatigable weakness. Both siblings had whole exome sequencing showing a homozygous variant (c.322C > T, p.Pro108Ser) of unknown significance in the epsilon subunit. Electromyography/nerve conduction study with repetitive nerve stimulation on one sibling showed a defect in neuromuscular junction transmission. Pseudoephedrine and fluoxetine for suspected slow-channel congenital myasthenic syndrome yielded no improvement. A trial of pyridostigmine led to clinical improvement. Given the clinical presentation, consanguinity, homozygous genetic variant, and response to pyridostigmine, we rationalize the homozygous variant (c.322C > T, p.Pro108Ser) in cholinergic receptor nicotinic epsilon subunit causes the primary acetylcholine-receptor deficiency congenital myasthenic syndrome.

• Authors: Cassie Chan, Lucy Emery, Caroline Maltese, Ashutosh Kumar, Ermal Aliu, Sunil Naik, Dustin Paul
• Journal: Child neurology open (Child Neurol Open) 2023 Jan-Dec Vol. 10 Pg. 2329048X231216432 ISSN: 2329-048X [Electronic] United States
• PMID: 38034490 (Publication Type: Case Reports)
• Copyright: © The Author(s) 2023.