title: A nonsense mutation (R220X) in the alpha-galactosidase A gene causes typical Fabry disease in both genders.
abstract: BACKGROUND
  Fabry disease is an X-linked recessive disorder resulting from a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). Chronic renal failure is an important cause of death in patients with Fabry disease. We report on patients with Fabry disease (a hemizygous male and his mother) due to a nonsense mutation (R220X) in the alpha-Gal A gene.
  
  
  METHODS
  The proband, a 41-year-old man, and his 71-year-old mother presented with renal and cardiac manifestations of Fabry disease. Histological examination and molecular analysis of the alpha-Gal A gene were performed.
  
  
  RESULTS
  Typical histological findings of Fabry disease were observed in a renal biopsy specimen from the proband and in renal and myocardial necropsy specimens from the mother. Sequencing of a full-length alpha-Gal A cDNA from the proband indicated a C-T transition at codon 220, resulting in substitution of the predictable termination for arginine (R220X). Examination of genomic alpha-Gal A DNA revealed that the proband was a hemizygote and the mother was a heterozygous carrier for the mutation.
  
  
  CONCLUSIONS
  This is the first detailed report of family members with Fabry disease due to a nonsense mutation (R220X) in the alpha-Gal A gene. Our study indicates that this mutation causes the typical disease in both genders.
authors.affiliation: Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Maki
authors.forename: A
authors.initials: A
authors.lastname: Komatsuda
authors.forename: H
authors.initials: H
authors.lastname: Wakui
authors.forename: Y
authors.initials: Y
authors.lastname: Oyama
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Ohtani
authors.forename: A
authors.initials: A
authors.lastname: Kigawa
authors.forename: N
authors.initials: N
authors.lastname: Aiba
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Motegi
authors.forename: A
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Sawada
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D018389:Codon, Nonsense / Q000235:genetics*; D000795:Fabry Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D010375:Pedigree; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D000519:alpha-Galactosidase