title: A candidate gene for autoimmune myasthenia gravis.
abstract: OBJECTIVE
  We sought to identify a causative mutation in a previously reported kindred with parental consanguinity and 5 of 10 siblings with adult-onset autoimmune myasthenia gravis.
  
  
  METHODS
  We performed genome-wide homozygosity mapping, and sequenced all known genes in the one region of extended homozygosity. Quantitative and allele-specific reverse transcriptase PCR (RT-PCR) were performed on a candidate gene to determine the RNA expression level in affected siblings and controls and the relative abundance of the wild-type and mutant alleles in a heterozygote.
  
  
  RESULTS
  A region of shared homozygosity at chromosome 13q13.3-13q14.11 was found in 4 affected siblings and 1 unaffected sibling. A homozygous single nucleotide variant was found in the 3'-untranslated region of the ecto-NADH oxidase 1 gene (ENOX1). No other variants likely to be pathogenic were found in genes in this region or elsewhere. The ENOX1 sequence variant was not found in 764 controls. Quantitative RT-PCR showed that expression of ENOX1 decreased to about 20% of normal levels in lymphoblastoid cells from individuals homozygous for the variant and to about 50% in 2 unaffected heterozygotes. Allele-specific RT-PCR showed a 55%-60% reduction in the level of the variant transcript in heterozygous cells due to reduced mRNA stability.
  
  
  CONCLUSIONS
  These results indicate that this sequence variant in ENOX1 may contribute to the familial autoimmune myasthenia in these patients.
authors: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Guida
authors: G
authors: Landouré
authors: Melanie A
authors: MA
authors: Knight
authors: Horia
authors: H
authors: Stanescu
authors: Addis A
authors: AA
authors: Taye
authors: Yijun
authors: Y
authors: Shi
authors: Oumarou
authors: O
authors: Diallo
authors: Janel O
authors: JO
authors: Johnson
authors: Dena
authors: D
authors: Hernandez
authors: Bryan J
authors: BJ
authors: Traynor
authors: Leslie G
authors: LG
authors: Biesecker
authors: Abdel
authors: A
authors: Elkahloun
authors: Carlo
authors: C
authors: Rinaldi
authors: Angela
authors: A
authors: Vincent
authors: Nick
authors: N
authors: Willcox
authors: Robert
authors: R
authors: Kleta
authors: Kenneth H
authors: KH
authors: Fischbeck
authors: Barrington G
authors: BG
authors: Burnett
mesh_terms: D000368:Aged; D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D003241:Consanguinity; D008040:Genetic Linkage; D006801:Humans; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D009157:Myasthenia Gravis / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D009097:Multienzyme Complexes; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases