Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders that give rise to a defect in neuromuscular transmission. We described here three patients with a characteristic phenotype of recessive CMS and presenting mutation in the gene encoding rapsyn (RAPSN). Familial analysis showed that one allelic mutation failed to be detected by direct sequencing. An allelic quantification on patient's DNA identified three novel multi-exon deletions of RAPSN. These three genomic rearrangements in RAPSN represent 15% of our CMS patients with RAPSN mutations and we emphasize that single-nucleotide polymorphism markers and a gene dosage method should be performed in addition to DNA direct sequencing analysis particularly when there is a genetic counselling issue.
- Congenital myasthenic syndrome
- chromosomic microdeletion
- loss of heterozygosity
- allele copy number
- molecular genetics
- neuromuscular disease
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Daniel Hantaï, Pascale Richard-co-last authors.
Funding ANR, AFM, Inserm, APHP.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the GH Pitié-Salpêtrière, Paris, France.
Provenance and peer review Not commissioned; externally peer reviewed.
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