title: Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family.
abstract: BACKGROUND
  Choline acetyltransferase (CHAT) gene mutations cause a rare presynaptic congenital myasthenic syndrome due to impaired acetylcholine resynthesis.
  
  
  METHODS
  We report 2 Kadazandusun brothers with novel heterozygous CHAT mutations.
  
  
  RESULTS
  The siblings were from a family of 7 children of nonconsanguineous parents, 3 who died from apneic crises. Both presented in infancy with ptosis and exertional limb weakness, but only 1 apnea episode was reported in the older sibling. The elder brother had a positive edrophonium test, and both were negative for acetylcholine receptor antibodies but improved with pyridostigmine treatment. A subsequent repetitive nerve stimulation test showed marked decremental response in the abductor digiti minimi only after prolonged ulnar nerve stimulation. Two novel CHAT gene mutations, p.Val306Leu and p.Ser704del were detected; the parents carried 1 mutation each.
  
  
  CONCLUSIONS
  Differences in survival demonstrate phenotypic variability within the same family and a relatively good long-term outcome of the surviving siblings.
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Joo-San
authors.initials: JS
authors.lastname: Tan
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Tomica
authors.initials: T
authors.lastname: Ambang
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Ahmad-Annuar
authors.affiliation: Department of Medicine, Hospital Queen Elizabeth, Kota Kinabalu, Sabah, Malaysia.
authors.forename: Giri Shan
authors.initials: GS
authors.lastname: Rajahram
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kum Thong
authors.initials: KT
authors.lastname: Wong
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Khean Jin
authors.initials: KJ
authors.lastname: Goh
mesh_terms: D044466:Asian People; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D006579:Heterozygote; D006801:Humans; D008296:Malaysia; D008297:Male; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D011729:Pyridostigmine Bromide / Q000627:therapeutic use; D035781:Siblings; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D002795:Choline O-Acetyltransferase; D011729:Pyridostigmine Bromide
keywords: CHAT; Kadazandusun; apneic episodes; choline acetyltransferase; congenital myasthenic syndrome; novel mutations