title: Mosaicism due to myeloid lineage restricted loss of heterozygosity as cause of spontaneous Rh phenotype splitting.
abstract: Spontaneous Rh phenotype alteration interferes with pretransfusion and prenatal blood group examinations and may potentially indicate hematologic disease. In this study, the molecular background of this biologic phenomenon was investigated. In 9 patients (3 with hematologic disease), routine RhD typing showed a mixture of D-positive and D-negative red cells not attributable to transfusion or hematopoietic stem-cell transplantation. In all patients, congenital and acquired chimerism was excluded by microsatellite analysis. In contrast to D-positive red cells, D-negative subpopulations were also negative for C or E in patients genotyped CcDdee or ccDdEe, respectively, which suggested the presence of erythrocyte precursors with an apparent homozygous cde/cde or hemizygous cde/- genotype. Except for one patient with additional Fy(b) antigen anomaly, no other blood group systems were affected. RH genotyping of single erythropoietic burst-forming units, combined with microsatellite analysis of blood, different tissues, sorted blood cell subsets, and erythropoietic burst-forming units, indicated myeloid lineage-restricted loss of heterozygosity (LOH) of variable chromosome 1 stretches encompassing the RHD/RHCE gene loci. Fluorescent in situ hybridization studies indicated that LOH was caused by either somatic recombination or deletion. Therefore, most cases of spontaneous Rh phenotype splitting appear to be due to hematopoietic mosaicism based on LOH on chromosome 1.
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria. guenther.goermoeczi@meduniwien.ac.at
authors.forename: Günther F
authors.initials: GF
authors.lastname: Körmöczi
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Dauber
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Legler
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Clausen
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritsch
authors.forename: Markus
authors.initials: M
authors.lastname: Raderer
authors.forename: Christoph
authors.initials: C
authors.lastname: Buchta
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Petzer
authors.forename: Diether
authors.initials: D
authors.lastname: Schönitzer
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Mayr
authors.forename: Christoph
authors.initials: C
authors.lastname: Gassner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D046528:Chimerism; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004912:Erythrocytes; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009030:Mosaicism; D022423:Myeloid Cells / Q000473:pathology*; D010641:Phenotype; D011995:Recombination, Genetic; D012204:Rh-Hr Blood-Group System / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System