1. ¹Department of Medicine, University of Hong Kong, Hong Kong, China
2. ²Department of Biochemistry, University of Hong Kong, Hong Kong, China
3. ³Genome Research Center, University of Hong Kong, Hong Kong, China
4. ⁴Department of Pathology, University of Hong Kong, Hong Kong, China

Correspondence: Dr Y-L Kwong, Department of Medicine, University of Hong Kong, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. E-mail: ylkwong@hkucc.hku.hk

Received 11 April 2007; Revised 18 June 2007; Accepted 19 June 2007; Published online 30 July 2007.

Abstract

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.