title: Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians.
abstract: BACKGROUND
  Age-related skewing of X-chromosome inactivation leading to glucose-6-phosphate dehydrogenase (G6PD) deficiency in elderly women in a population with prevalent G6PD gene mutations was investigated.
  
  
  METHODS
  G6PD activity was measured biochemically. G6PD mutations were detected by polymerase chain reaction (PCR) and allele-specific extension, and analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and Sequenom MassARRAY. X-chromosome inactivation was quantified by semiquantitative PCR for the HUMARA gene, before and after HpaII digestion.
  
  
  RESULTS
  In 173 women (median age: 90 years; range, 80-107 years), 18 heterozygotes for G6PD mutations were identified. Three heterozygotes were G6PD deficient, owing to skewed X-chromosome inactivation affecting the wild-type allele. Fifteen heterozygotes, with skewing apparently affecting the mutant alleles, had normal but significantly lower G6PD levels. At 1.73%, G6PD deficiency was significantly more frequent than expected from population screening at birth.
  
  
  CONCLUSIONS
  Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
authors.affiliation: Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong.
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Au
authors.forename: Veronica
authors.initials: V
authors.lastname: Lam
authors.forename: Annie
authors.initials: A
authors.lastname: Pang
authors.forename: Wing-Man
authors.initials: WM
authors.lastname: Lee
authors.forename: Jess L C
authors.initials: JL
authors.lastname: Chan
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
authors.forename: Edmond S
authors.initials: ES
authors.lastname: Ma
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D009154:Mutation; D010641:Phenotype; D049951:X Chromosome Inactivation
chemical_list: D005954:Glucosephosphate Dehydrogenase