Dataset Information

No Hot Spot Mutations CHRNE c.1327 delG, CHAT c.914T>C, and RAPSN c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome.

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. Materials & 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.

SUBMITTER: Parvizi Omran S

PROVIDER: S-EPMC6451864 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

No Hot Spot Mutations <i>CHRNE</i> c.1327 delG, <i>CHAT</i> c.914T>C, and <i>RAPSN</i> c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome.

Parvizi Omran Sima S Houshmand Massod M Dominic Donkor D Farjami Zahra Z Karimzadeh Parvaneh P

Iranian journal of child neurology 20190101 2

<h4>Objectives</h4>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.<h4>Materials & methods</h4>Sixteen patients were screened in Taban Clinic, Tehran, Iran from 2014 to 2015 for the hot spot mutations in known CMSs genes (<i>CHRNE, CHAT</i>, <i>RAPSN</i>) based on clinical data. PCR was performed a ...[more]

PMID: 31037086

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Project description:Congenital myasthenic syndromes are inherited disorders that arise from impaired signal transmission at the neuromuscular junction. Mutations in at least 20 genes are known to lead to the onset of these conditions. Four of these, ALG2, ALG14, DPAGT1 and GFPT1, are involved in glycosylation. Here we identify a fifth glycosylation gene, GMPPB, where mutations cause congenital myasthenic syndrome. First, we identified recessive mutations in seven cases from five kinships defined as congenital myasthenic syndrome using decrement of compound muscle action potentials on repetitive nerve stimulation on electromyography. The mutations were present through the length of the GMPPB, and segregation, in silico analysis, exon trapping, cell transfection followed by western blots and immunostaining were used to determine pathogenicity. GMPPB congenital myasthenic syndrome cases show clinical features characteristic of congenital myasthenic syndrome subtypes that are due to defective glycosylation, with variable weakness of proximal limb muscle groups while facial and eye muscles are largely spared. However, patients with GMPPB congenital myasthenic syndrome had more prominent myopathic features that were detectable on muscle biopsies, electromyography, muscle magnetic resonance imaging, and through elevated serum creatine kinase levels. Mutations in GMPPB have recently been reported to lead to the onset of muscular dystrophy dystroglycanopathy. Analysis of four additional GMPPB-associated muscular dystrophy dystroglycanopathy cases by electromyography found that a defective neuromuscular junction component is not always present. Thus, we find mutations in GMPPB can lead to a wide spectrum of clinical features where deficit in neuromuscular transmission is the major component in a subset of cases. Clinical recognition of GMPPB-associated congenital myasthenic syndrome may be complicated by the presence of myopathic features, but correct diagnosis is important because affected individuals can respond to appropriate treatments.

Dataset Information

No Hot Spot Mutations CHRNE c.1327 delG, CHAT c.914T>C, and RAPSN c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome.

Publications

No Hot Spot Mutations <i>CHRNE</i> c.1327 delG, <i>CHAT</i> c.914T>C, and <i>RAPSN</i> c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome.

Similar Datasets

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