Genetic basis and phenotypic features of congenital myasthenic syndromes

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Citations (Scopus)

Abstract

The congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. The disease proteins reside in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region, or at multiple sites at the neuromuscular junction as well as in other tissues. Targeted mutation analysis by Sanger or exome sequencing has been facilitated by characteristic phenotypic features of some CMS. No fewer than 20 disease genes have been recognized to date. In one-half of the currently identified probands, the disease stems from mutations in genes encoding subunits of the muscle form of the acetylcholine receptor (CHRNA1, CHRNB, CHRNAD1, and CHRNE). In 10–14% of the probands the disease is caused by mutations in RAPSN, DOK 7, or COLQ, and in 5% by mutations in CHAT. Other less frequently identified disease genes include LAMB2, AGRN, LRP4, MUSK, GFPT1, DPAGT1, ALG2, and ALG 14 as well as SCN4A, PREPL, PLEC1, DNM2, and MTM1. Identification of the genetic basis of each CMS is important not only for genetic counseling and disease prevention but also for therapy, because therapeutic agents that benefit one type of CMS can be harmful in another.

Original languageEnglish (US)
Title of host publicationNeurogenetics, Part II
PublisherElsevier B.V.
Pages565-589
Number of pages25
ISBN (Print)9780444640765
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Publication series

NameHandbook of Clinical Neurology
Volume148
ISSN (Print)0072-9752
ISSN (Electronic)2212-4152

Fingerprint

Congenital Myasthenic Syndromes
Mutation
Genes
Exome
Inborn Genetic Diseases
Neuromuscular Junction
Genetic Counseling
Presynaptic Terminals
Cholinergic Receptors
Basement Membrane
Safety
Muscles
Therapeutics
Proteins

Keywords

  • congenital myasthenic syndromes
  • EMG
  • exome sequencing
  • mutation analysis
  • neuromuscular junction
  • neuromuscular transmission
  • phenotypic clues
  • therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Engel, A. G. (2018). Genetic basis and phenotypic features of congenital myasthenic syndromes. In Neurogenetics, Part II (pp. 565-589). (Handbook of Clinical Neurology; Vol. 148). Elsevier B.V.. https://doi.org/10.1016/B978-0-444-64076-5.00037-5

Genetic basis and phenotypic features of congenital myasthenic syndromes. / Engel, Andrew G.

Neurogenetics, Part II. Elsevier B.V., 2018. p. 565-589 (Handbook of Clinical Neurology; Vol. 148).

Research output: Chapter in Book/Report/Conference proceedingChapter

Engel, AG 2018, Genetic basis and phenotypic features of congenital myasthenic syndromes. in Neurogenetics, Part II. Handbook of Clinical Neurology, vol. 148, Elsevier B.V., pp. 565-589. https://doi.org/10.1016/B978-0-444-64076-5.00037-5
Engel AG. Genetic basis and phenotypic features of congenital myasthenic syndromes. In Neurogenetics, Part II. Elsevier B.V. 2018. p. 565-589. (Handbook of Clinical Neurology). https://doi.org/10.1016/B978-0-444-64076-5.00037-5
Engel, Andrew G. / Genetic basis and phenotypic features of congenital myasthenic syndromes. Neurogenetics, Part II. Elsevier B.V., 2018. pp. 565-589 (Handbook of Clinical Neurology).
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