No Hot Spot Mutations CHRNE c.1327 delG, CHAT c.914T>C, and RAPSN c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome
Iranian Journal of Child Neurology,
Vol. 13 No. 2 (2019),
4 March 2019
,
Page 135-143
https://doi.org/10.22037/ijcn.v13i2.18796
Abstract
Abstract
Objectives
We aimed to perform genetic testing and clinical data of patients with Congenital Myasthenic Syndrome, a rare disorder caused by mutations in genes encoding molecules expressed in the neuromuscular junction and constitutes fatigable muscle weakness.
Methods
Sixteen patients were screened in Taban Clinic, Tehran, Iran from 2014 to 2015 for the hot spot mutations in known CMSs genes (CHRNE, CHAT, RAPSN) based on clinical data. PCR was performed and then direct DNA sequencing was done for mutation identification.
Results
Most patients represented the criteria of Congenital Myasthenic Syndrome in view of early ptosis, motor delay, normal mental development, easy fatigability, decrement in repetitive nerve stimulation test of EMG-NCV and a negative result for antibody against of acetylcholine receptor. No variations were found in the mutational analysis of the CHRNE gene. Analysis of CHAT gene revealed c.358G>A (P. A120T) variation in 9 patients. In the gene RAPSN, polymorphism c.456T>C )P.Y152Y) and polymorphism c.193-15C>T (IVS1-15C>T) were identified in 11 and one patients, respectively.
Conclusion
The common founder mutations of involved genes in CMSs could be very rare among ethnic Iranian. Screening of the entire genes would be efficient to distinguish the specific mutations in specific ethnicity.
- Congenital myasthenic syndrome
- CHRNE
- CHAT
- Rapsyn
- Hot spot mutation
How to Cite
References
Natera-de Benito D, Bestué M, Vilchez J, Evangelista T, Töpf A, García-Ribes A, et al. Long-term follow-up in patients with congenital myasthenic syndrome due to RAPSN mutations. Neuromuscular Disord 2016;26(2):153-9.
Milone M, Shen X, Selcen D, Ohno K, Brengman J, Iannaccone S, et al. Myasthenic syndrome due to defects in rapsyn Clinical and molecular findings in 39 patients. Neurology 2009;73(3):228-35.
Pavone P, Polizzi A, Longo MR, Romano K, Vecchio M, Praticò AD, et al. Congenital myasthenic syndromes: Clinical and molecular report on 7 Sicilian patients. J Pediatr Neurosci 2013;8(1):19.
Liu Z, Fang F, Ding C, Zhang W, Deng J, Chen C, et al. Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases. Zhonghua Er ke Za Zhi 2018;56(3):216-20.
Yasaki E, Prioleau C, Barbier J, Richard P, Andreux F, Leroy J-P, et al. Electrophysiological and morphological characterization of a case of autosomal recessive congenital myasthenic syndrome with acetylcholine receptor deficiency due to a N88K rapsyn homozygous mutation. Neuromuscul Disord 2004;14(1):24-32.
Abicht A, Dusl M, Gallenmüller C, Guergueltcheva V, Schara U, Della Marina A, et al. Congenital myasthenic syndromes: Achievements and limitations of phenotype‐guided gene‐after‐gene sequencing in diagnostic practice: A study of 680 patients. Hum Mutat 2012;33(10):1474-84.
Müller J, Baumeister S, Rasic V, Krause S, Todorovic S, Kugler K, et al. Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations. Neurology 2006;67(7):1159-64.
Karcagi V, Tourrnev I, Schmidt C, Herczegfalvi A, Guergueltcheva V, Litvinenko I, et al. editors. Congenital myasthenic syndrome in southeastern European Roma (Gypsies). Acta Myologica 2001; 20:231-237.
Müller J, Mildner G, Müller–Felber W, Schara U, Krampfl K, Petersen B, et al. Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients. Neurology 2003;60(11):1805-10.
Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, et al. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A 2001;98(4):2017-22.
Müller J, Abicht A, Burke G, Cossins J, Richard P, Baumeister S, et al. The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder. J Med Genet 2004;41(8):e104-e.
Aharoni S, Sadeh M, Shapira Y, Edvardson S, Daana M, Dor-Wollman T, et al. Congenital myasthenic syndrome in Israel: genetic and clinical characterization. Neuromuscular Disord 2017;27(2):136-40.
Natera-de Benito D, Domínguez-Carral J, Muelas N, Nascimento A, Ortez C, Jaijo T, et al. Phenotypic heterogeneity in two large Roma families with a congenital myasthenic syndrome due to CHRNE 1267delG mutation. A long-term follow-up. Neuromuscul Disord 2016;26(11):789-95.
Ohno K, Engel AG, Shen X-M, Selcen D, Brengman J, Harper CM, et al. Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. Am J Hum Genet 2002;70(4):875-85.
Burke G, Cossins J, Maxwell S, Owens G, Vincent A, Robb S, et al. Rapsyn mutations in hereditary myasthenia Distinct early-and late-onset phenotypes. Neurology 2003;61(6):826-8.
Burke G, Cossins J, Maxwell S, Robb S, Nicolle M, Vincent A, et al. Distinct phenotypes of congenital acetylcholine receptor deficiency. Neuromuscular Disord 2004;14(6):356-64.
Richard P, Gaudon K, Andreux F, Yasaki E, Prioleau C, Bauche S, et al. Possible founder effect of rapsyn N88K mutation and identification of novel rapsyn mutations in congenital myasthenic syndromes. J Med Genet 2003;40(6):e81-e.
Mihaylova V, Scola R, Gervini B, Lorenzoni P, Kay C, Werneck L, et al. Molecular characterisation of congenital myasthenic syndromes in Southern Brazil. J Neurol Neurosurg Psychiatry 2010:jnnp. 2009.177816.
Azuma Y, Nakata T, Tanaka M, Shen X-M, Ito M, Iwata S, et al. Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits. Neuromuscular Disord 2015;25(1):60-9.
- Abstract Viewed: 195 times