Identification of a Novel ASAH1 Gene Mutation in Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy Novel ASAH1 Gene Mutation in SMA-PME
Iranian Journal of Child Neurology,
Vol. 18 No. 3 (2024),
22 May 2024
,
Page 131-135
https://doi.org/10.22037/ijcn.v18i3.44081
Abstract
Spinal muscular atrophy (SMA) with progressive myoclonic epilepsy (PME) affects the nervous system. Symptoms appear in early childhood and include muscle weakness, difficulty walking, seizures, and cognitive decline. Despite introducing various therapies to restore acid ceramidase function or reduce ceramide accumulation and gene therapy to correct genetic mutations, there are still unknown underlying molecular mechanisms related to this disorder. This article reports a novel variant c.118G>C in the ASAH1 gene. The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epileptic discharge. A significant temporal interval was observed between the initial diagnosis of SMA and the subsequent manifestation of myoclonic seizures. The proband was genetically assessed through whole exome sequencing (WES) followed by variant confirmation and bioinformatics analysis. According to this article’s findings and previous research, further diagnostic testing and management are needed to determine the severity and progression of the patient’s condition
- Spinal Muscular Atrophy, Progressive Myoclonic Epilepsy, Gene Mutation
How to Cite
References
Yu FP, Amintas S, Levade T, Medin JA. Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet journal of rare diseases. 2018;13(1):1-19.
Liyanage DS, Pathberiya LS, Gooneratne IK, Vithanage KK, Gamage R. Association of type IV spinal muscular atrophy (SMA) with myoclonic epilepsy within a single family. International Archives of Medicine. 2014;7(1):1-4.
Dyment D, Sell E, Vanstone M, Smith A, Garandeau D, Garcia V, et al. Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy. Clinical genetics. 2014;86(6):558-63.
Gebai A, Gorelik A, Li Z, Illes K, Nagar B. Structural basis for the activation of acid ceramidase. Nature communications. 2018;9(1):1621.
Najafi A, Tasharrofi B, Zandsalimi F, Rasulinezhad M, Ghahvechi Akbari M, Zamani G, et al. Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME): three new cases and review of the mutational spectrum. Italian journal of pediatrics. 2023;49(1):64.
Jankovic J, Rivera VM. Hereditary myoclonus and progressive distal muscular atrophy. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1979;6(3):227-31.
Zhou J, Tawk M, Tiziano FD, Veillet J, Bayes M, Nolent F, et al. Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. The American Journal of Human Genetics. 2012;91(1):5-14.
Jankovic J, Rivera V. Hereditary myoclonus and progressive muscular atrophy: a new syndrome. Transactions of the American Neurological Association. 1978;103:116-8.
Karimzadeh P, Najmabadi H, Lochmuller H, Babaee M, Dehdahsi S, Miryounesi M, et al. Five patients with spinal muscular atrophy-progressive myoclonic epilepsy (SMA-PME): a novel pathogenic variant, treatment and review of the literature. 2022.
- Abstract Viewed: 277 times