G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors.

To determine whether during hematopoietic stem cell transplantation (HSCT), X-chromosome inactivation (lyonization) of donor HSC might change after engraftment in recipients, the glucose-6-phosphate dehydrogenase (G6PD) gene of 180 female donors was genotyped by PCR/allele-specific primer extension, and MALDI-TOF mass spectrometry/Sequenom MassARRAY analysis. X-inactivation was determined by semiquantitative PCR for the HUMARA gene before/after HpaII digestion. X-inactivation was preserved in most cases post-HSCT, although altered skewing of lyonization might occur to either of the X-chromosomes. Among pre-HSCT clinicopathologic parameters analyzed, only recipient gender significantly affected skewing. Seven donors with normal G6PD biochemically but heterozygous for G6PD mutants were identified. Owing to lyonization changes, some donor-recipient pairs showed significantly different G6PD levels. In one donor-recipient pair, extreme lyonization affecting the wild-type G6PD allele occurred, causing biochemical G6PD deficiency in the recipient. In HSCT from asymptomatic female donors heterozygous for X-linked recessive disorders, altered lyonization might cause clinical diseases in the recipients.

Increased alpha 7 nicotinic acetylcholine receptor protein levels in Alzheimer's disease patients.

We compared the intact alpha7 nicotinic acetylcholine receptor (alpha7nAChR) protein levels in the peripheral blood leukocytes in 15 Alzheimer's disease (AD) patients and 13 normal elderly control subjects. Demographic data and Mini-Mental State Examination (MMSE) scores were obtained. Western blot analysis for alpha7nAChR protein levels in peripheral blood leukocytes was performed. There were no significant differences in sex and age between the AD and control groups. The mean MMSE score of the AD subjects was significantly lower than that of the normal control subjects (15.4 +/- 5.5 vs. 28.5 +/- 1.9 respectively; p < 0.001). The median value of normalized alpha7nAChR protein levels (optical density, arbitrary unit) of the AD group was significantly higher than that of the normal control group (0.6923 vs. 0.4803 respectively; p = 0.045, Mann-Whitney U test). The normalized alpha7nAChR protein levels showed a significant inverse correlation with the MMSE scores (Spearman rho = -0.45; p = 0.016; n = 28). Receiver Operating Characteristic curve analyses showed that the area under curve was 0.72 (95% CI 0.52- 0.87). If the cut-off of the alpha7nAChR protein level was >0.312, the sensitivity, specificity, positive predictive value and negative predictive value would be 80, 39, 60 and 63%, respectively. These findings showed that the alpha7nAChR protein levels would be a potentially useful diagnostic marker for AD.