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. CONCLUSION: Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
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. CONCLUSION: Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
Authors: Shivang S Shah; Seidina A S Diakite; Karim Traore; Mahamadou Diakite; Dominic P Kwiatkowski; Kirk A Rockett; Thomas E Wellems; Rick M Fairhurst Journal: Sci Rep Date: 2012-03-05 Impact factor: 4.379
Authors: Chani J Hodonsky; Deepti Jain; Ursula M Schick; Jean V Morrison; Lisa Brown; Caitlin P McHugh; Claudia Schurmann; Diane D Chen; Yong Mei Liu; Paul L Auer; Cecilia A Laurie; Kent D Taylor; Brian L Browning; Yun Li; George Papanicolaou; Jerome I Rotter; Ryo Kurita; Yukio Nakamura; Sharon R Browning; Ruth J F Loos; Kari E North; Cathy C Laurie; Timothy A Thornton; Nathan Pankratz; Daniel E Bauer; Tamar Sofer; Alex P Reiner Journal: PLoS Genet Date: 2017-04-28 Impact factor: 6.020