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Multiexon deletions account for 15% of congenital myasthenic syndromes with RAPSN mutations after negative DNA sequencing
  1. Karen Gaudon1,
  2. Isabelle Pénisson-Besnier2,
  3. Brigitte Chabrol3,
  4. Françoise Bouhour4,
  5. Laurence Demay1,
  6. Asma Ben Ammar5,6,
  7. Stéphanie Bauché5,7,
  8. Christophe Vial4,
  9. Guillaume Nicolas2,
  10. Bruno Eymard5,7,8,
  11. Daniel Hantaï5,7,8,
  12. Pascale Richard1,9
  1. 1AP-HP, UF Cardiogénétique et Myogénétique, Service de Biochimie Métabolique, GH Pitié Salpêtrière, Paris, France
  2. 2Centre de référence Maladies Neuromusculaires Nantes-Angers, Département de Neurologie, CHU Angers, France
  3. 3AP-HM, Service de Neuropédiatrie, Hôpital La Timone-Enfants, Marseille, France
  4. 4Service d‘Electroneuromyographie et Pathologies Neuromusculaires, Hôpital Neurologique, GH Lyon Est, Bron, France
  5. 5Inserm, U975, CRICM, GH Pitié Salpêtrière, Paris, France
  6. 6INN, La Rabta, Université Tunis El Manar, Tunis, Tunisia
  7. 7UPMC, Université Pierre et Marie Curie, Paris, France
  8. 8AP-HP, Centre de Référence en Pathologie Neuromusculaire Paris-Est, GH Pitié Salpêtrière, Paris, France
  9. 9Inserm, U956, UPMC, Université Pierre et Marie Curie, Paris, France
  1. Correspondence to Dr Daniel Hantaï, INSERM U.975 - Institut de Myologie, Hôpital de la Salpêtrière, 47, Boulevard de l'Hôpital, Paris 75013, France; daniel.hantai{at}upmc.fr

Abstract

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
  • rapsyn
  • chromosomic microdeletion
  • loss of heterozygosity
  • allele copy number
  • molecular genetics
  • neurology
  • neuromuscular disease
  • neurosciences

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Footnotes

  • DH and PR are 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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