Bi-allelic Mutations in CHRNE Cause Autosomal-Recessive Slow-Channel Congenital Myasthenic Syndrome

Introduction: The slow-channel congenital myasthenic syndrome (SCCMS) is a postsynaptic form of congenital myasthenic syndromes (CMSs), a clinically heterogeneous group of disorders caused by genetic defects leading to a prolonged signal transmission at the endplate.Methods: We report clinical and molecular data of a Lor family in which the presentation of a progressive proximal-distal weakness with ocular involvement led to a number of mistaken clinical diagnoses whose treatment trials appeared with no clinical benefit.Results: A comprehensive genetic study which included whole-exome sequencing identified a compound heterozygous splicing/missense substitutions (c.1032+1G> C/c.C422T, p.P141L) in the ε subunit of the acetylcholine receptor (CHRNE) that was consistent with clinical weakness in the patient.Discussion: SCCMS is characterized by a broad and heterogeneous clinical phenotype in which the disease features can highly mimic acquired disorders but no clinical response to their routine therapy. The identification of a couple of CHRNE mutations allowed to make the definitive diagnosis of CMS in this family and contributed to treatment revision, as, unlike acquired myasthenic syndromes, it perfectly responded to fluoxetine therapy, a long-lived open-channel blocker.

کلیدواژه ها:

Slow-channel congenital myasthenic syndrome ، Whole-exome sequencing ، CHRNE mutation ، Fluoxetine therapy