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.
Department of Medicine, University of Hong Kong, Hong Kong, China.
W-Y
WY
Au
A
A
Pang
K K Y
KK
Lam
Y-Q
YQ
Song
W-M
WM
Lee
J C C
JC
So
Y-L
YL
Kwong
D000328:Adult; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D017931:DNA Primers; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000097:blood / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics; D012016:Reference Values; D015183:Restriction Mapping; D035781:Siblings; D014019:Tissue Donors / Q000706:statistics & numerical data
C410798:AR protein, human; D017931:DNA Primers; D011944:Receptors, Androgen; D005954:Glucosephosphate Dehydrogenase