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

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.

2020 ◽  
Vol 6 (4) ◽  
pp. e468
Author(s):  
Szabolcs Szelinger ◽  
Jonida Krate ◽  
Keri Ramsey ◽  
Samuel P. Strom ◽  
Perry B. Shieh ◽  
...  

ObjectiveDescription of a new variant of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene causing congenital myasthenic syndrome (CMS) in 3 children from 2 unrelated families.MethodsMuscle biopsies, EMG, and whole-exome sequencing were performed.ResultsAll 3 patients presented with congenital hypotonia, muscle weakness, respiratory insufficiency, head lag, areflexia, and gastrointestinal dysfunction. Genetic analysis identified a homozygous frameshift insertion in the GFPT1 gene (NM_001244710.1: c.686dupC; p.Arg230Ter) that was shared by all 3 patients. In one of the patients, inheritance of the variant was through uniparental disomy (UPD) with maternal origin. Repetitive nerve stimulation and single-fiber EMG was consistent with the clinical diagnosis of CMS with a postjunctional defect. Ultrastructural evaluation of the muscle biopsy from one of the patients showed extremely attenuated postsynaptic folds at neuromuscular junctions and extensive autophagic vacuolar pathology.ConclusionsThese results expand on the spectrum of known loss-of-function GFPT1 mutations in CMS12 and in one family demonstrate a novel mode of inheritance due to UPD.


2020 ◽  
Vol 91 (8) ◽  
pp. 898-900 ◽  
Author(s):  
Andoni Echaniz-Laguna ◽  
Valérie Biancalana ◽  
Aleksandra Nadaj-Pakleza ◽  
Emmanuel Fournier ◽  
Emma Matthews ◽  
...  

2017 ◽  
Vol 18 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Mert Karakaya ◽  
Ozge Ceyhan-Birsoy ◽  
Alan H. Beggs ◽  
Haluk Topaloglu

1995 ◽  
Vol 58 (2) ◽  
pp. 147-151 ◽  
Author(s):  
Kathleen Harrison ◽  
Katerina Eisenger ◽  
Kwame Anyane-Yeboa ◽  
Stephen Brown

Author(s):  
Paulo José Lorenzoni ◽  
Renata Dal-Pra Ducci ◽  
Raquel Cristina Arndt ◽  
Nyvia Milicio Coblinski Hrysay ◽  
Otto Jesus Hernandez Fustes ◽  
...  

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.


2018 ◽  
Vol 133 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Jesica Carina Guzmán-Alberto ◽  
Gabriela Martínez-Cortes ◽  
Héctor Rangel-Villalobos

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