A newly identified chromosomal microdeletion of the rapsyn gene causes a congenital myasthenic syndrome

Neuromuscul Disord. 2004 Nov;14(11):744-9. doi: 10.1016/j.nmd.2004.06.010.


The objective is mutation analysis of the RAPSN gene in a patient with sporadic congenital myasthenic syndrome (CMS). Mutations in various genes encoding proteins expressed at the neuromuscular junction may cause CMS. Most mutations affect the epsilon subunit gene of the acetylcholine receptor (AChR) leading to endplate AChR deficiency. Recently, mutations in the RAPSN gene have been identified in several CMS patients with AChR deficiency. In most patients, RAPSN N88K was identified, either homozygously or heteroallelic to a second missense mutation. A sporadic CMS patient from Germany was analyzed for RAPSN mutations by RFLP, long-range PCR and sequence analysis. Clinically, the patient presents with an early onset CMS, associated with arthrogryposis multiplex congenita, recurrent episodes of respiratory insufficiency provoked by infections, and a moderate general weakness, responsive to anticholinesterase treatment. The mutation RAPSN N88K was found heterozygously to a large deletion of about 4.5 kb disrupting the RAPSN gene. Interestingly, an Alu-mediated unequal homologous recombination may have caused the deletion. We hypothesize that numerous interspersed Alu elements may predispose the RAPSN locus for genetic rearrangements.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Chromosomes
  • DNA Mutational Analysis / methods
  • Gene Deletion*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Male
  • Muscle Proteins / genetics*
  • Myasthenic Syndromes, Congenital / genetics*
  • Neuromuscular Junction / metabolism
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • RNA, Messenger / biosynthesis
  • Receptors, Cholinergic / deficiency
  • Receptors, Cholinergic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods


  • Muscle Proteins
  • RNA, Messenger
  • Receptors, Cholinergic
  • peripheral membrane protein 43K