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

This is the authors' abstract. We don't add key points for this paper.

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.