Slow-Channel Congenital Myasthenic Syndrome due to a Novel Mutation in the Acetylcholine Receptor Alpha Subunit in a South Asian: A Case Report

Article type: Case Report

Authors: Gooneratne, Inuka Kishara^{a; *} | Nandasiri, Shanika^a | Maxwell, Susan^b | Webster, Richard^b | Cossins, Judith^b | Beeson, David^b | Gunaratne, Kamal^a | Herath, Lalinka^c | Senanayake, Sunethra^a | Chang, Thashi^{a; d}

Affiliations: [a] National Hospital of Sri Lanka, Colombo, Sri Lanka | [b] Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom | [c] Human Genetics Unit, University of Colombo, Colombo, Sri Lanka | [d] Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

Correspondence: [*] Correspondence to: Inuka Kishara Gooneratne, 10/1 Borella Cross Road, Colombo 8, Sri Lanka. Tel.: +94 112773662903; E-mail: [email protected].

Abstract: Congenital myasthenic syndromes (CMS) result from genetic mutations that cause aberrations in structure and/or function of proteins involved in neuromuscular transmission. The slow-channel CMS (SCCMS) is an autosomal dominant postsynaptic defect caused by mutations in genes encoding alpha, beta, delta, or epsilon subunits of the acetylcholine receptor resulting in a functional defect which is an increase of the opening time of the receptor. We report a case of SCCMS due to a heterozygous mutation in the M2 domain of the AChR alpha subunit - CHRNA1:ENST00000348749.6:exon7:c.806T>G:p.Val269Gly and corresponding kinetic defect. A substitution of valine with phenylalanine in the same position has been previously described. This is the first reported case of a new CHRNA1 variant in a patient with SCCMS from South Asia. We also highlight the phenotype that would favour a genetic basis over an autoimmune one, in an adult presenting with fatigable weakness.

Keywords: Congenital myasthenic syndrome, slow channel syndrome, acetylcholine receptor alpha subunit gene

DOI: 10.3233/JND-200566

Journal: Journal of Neuromuscular Diseases, vol. 8, no. 1, pp. 163-167, 2021