[SMC] A Novel Homozygous Variant in the CHRNE Gene in 2 Siblings with Congenital Myasthenic Syndrome
Posté : 30 nov. 2023 12:00
Child Neurol Open. 2023 Nov 28;10:2329048X231216432. doi: 10.1177/2329048X231216432. eCollection 2023 Jan-Dec.
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.
PMID:38034490 | PMC:PMC10685742 | DOI:10.1177/2329048X231216432
Source: https://pubmed.ncbi.nlm.nih.gov/3803449 ... 8&v=2.18.0