Dataset Information

Congenital myasthenic syndrome caused by a frameshift insertion mutation in GFPT1.

ABSTRACT:

Objective

Description 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.

Methods

Muscle biopsies, EMG, and whole-exome sequencing were performed.

Results

All 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.

Conclusions

These 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.

SUBMITTER: Szelinger S

PROVIDER: S-EPMC7357421 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Congenital myasthenic syndrome caused by a frameshift insertion mutation in <i>GFPT1</i>.

Szelinger Szabolcs S Krate Jonida J Ramsey Keri K Strom Samuel P SP Shieh Perry B PB Lee Hane H Belnap Newell N Balak Chris C Siniard Ashley L AL Russell Megan M Richholt Ryan R Both Matt De M Claasen Ana M AM Schrauwen Isabelle I Nelson Stanley F SF Huentelman Matthew J MJ Craig David W DW Yang Samuel P SP Moore Steven A SA Sivakumar Kumaraswamy K Narayanan Vinodh V Rangasamy Sampathkumar S

Neurology. Genetics 20200630 4

<h4>Objective</h4>Description of a new variant of the glutamine-fructose-6-phosphate transaminase 1 (<i>GFPT1</i>) gene causing congenital myasthenic syndrome (CMS) in 3 children from 2 unrelated families.<h4>Methods</h4>Muscle biopsies, EMG, and whole-exome sequencing were performed.<h4>Results</h4>All 3 patients presented with congenital hypotonia, muscle weakness, respiratory insufficiency, head lag, areflexia, and gastrointestinal dysfunction. Genetic analysis identified a homozygous framesh ...[more]

PMID: 32754643

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