scholarly journals Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A

2018 ◽  
Vol 6 (3) ◽  
pp. 434-440 ◽  
Author(s):  
Ricardo A. Maselli ◽  
Jessica Vázquez ◽  
Leah Schrumpf ◽  
Juan Arredondo ◽  
Marian Lara ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Sequence Variants ◽  
Myasthenic Syndrome

scholarly journals Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

2021 ◽  
Author(s):  
Paulo José Lorenzoni ◽  
Renata Dal-Pra Ducci ◽  
Raquel Cristina Arndt ◽  
Nyvia Milicio Coblinski Hrysay ◽  
Otto Jesus Hernandez Fustes ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Myasthenia Gravis ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Previous Diagnosis ◽  
Seronegative Myasthenia Gravis ◽  
Single Center Study ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Variants ◽  
Brazilian Cohort

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of ‘double’ SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in ‘double’ SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with ‘double’ SNMG in whom differential diagnosis is recommended.

scholarly journals A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 821
Author(s):  
Olga Shchagina ◽  
Ludmila Bessonova ◽  
Igor Bychkov ◽  
Tatiana Beskorovainaya ◽  
Aleksander Poliakov
Keyword(s):  
Uniparental Disomy ◽  
Missense Variant ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Chromosome 2 ◽  
Loss Of Function ◽  
Maternal Uniparental Disomy ◽  
Healthy Sibling ◽  
Myasthenic Syndrome ◽  
The Moment

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes.

scholarly journals CHRNE compound heterozygous mutations in congenital myasthenic syndrome

Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0347
Author(s):  
Kunfang Yang ◽  
Hongyi Cheng ◽  
Fang Yuan ◽  
Linyi Meng ◽  
Rongrong Yin ◽  
...  
Keyword(s):  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Mutations

scholarly journals Congenital Myasthenic Syndrome Due to Compound Heterozygous Mutations in the GFPT1 Gene

2020 ◽  
Author(s):  
Yanfang Jiang ◽  
Siwen Liu ◽  
Chunyan Wang ◽  
Yan Yu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitor ◽  
Neuromuscular Disorders ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Blurred Vision ◽  
Gene Encoding ◽  
Limb Weakness ◽  
Repetitive Nerve Stimulation ◽  
Muscle Action Potential ◽  
Myasthenic Syndrome

Abstract Congenital myasthenic syndrome (CMS) is a heterogeneous group of hereditary neuromuscular disorders associated with neuromuscular junction (NMJ) dysfunction. Here, we report the genetic variants and clinical follow-up of one individual suffering from CMS. The proband presented with limb weakness, and symptoms worsened after limb activities. In addition, decreases in muscle action potential were observed with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but the patient did not experience drooping eyelids or blurred vision. Trio whole exome sequencing was performed for the proband and his parents. We found two different heterozygous missense variants (c.331C>T; p.Arg111Cys and c.1428G>C; p.Lys476Asn) in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in this patient with autosomal recessive CMS, of which one was novel. The new c.1428G>C; p.Lys476Asn variant has not been previously reported, and has not been recorded in the ClinVar dataset or the gnomAD global population dataset. The phenotypes （proximal muscle weakness and fatigue while ocular and facial involvement is only minimal，limb-girdle weakness and fatigue.，beneficial and sustained response to acetylcholinesterase inhibitor treatment）of the proband were consistent with those previously reported for CMS. Our study provides important information for the diagnosis and treatment of patients with CMS.

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