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E.M. Dauber et al.
Figure 3. Minimal expansion and cellu- lar/tissue distribution of loss of het- erozygosity (LOH) on 1p of proposita A and B. Chromosomal positions of the RHD/RHCE genes and the investigated chromosome 1 microsatellite loci are shown. The vertical arrows indicate the chromosomal 1p expansion of LOH. In the insert, the cells and tissues with or without LOH are specified. BFU-E: ery- thropoietic burst-forming units; n.a.: not available.
deletion on their altered 1p that would be recognized by only one RH-FISH signal, as demonstrated previously.4 Instead, they appear to have retained RH loci on both 1p, not distinguishable from normal cells in this assay. The mechanism of the mixed-field agglutination in serological Rhc typing is, therefore, probably a somatic recombina- tion with partial chromosome loss followed by a duplica- tion.
Further studies designed to identify the cell lines and tis- sues that were affected by LOH revealed a differential configuration in the 2 propositae (see insert of Figure 3). In proposita B, LOH was observed in a lineage-specific distri- bution, occurring in a fraction of myeloid cell subsets but not in lymphoid compartments or non-hematopoietic tis- sues. Accordingly, only some, but not all, of the studied BFU-E colonies showed LOH. These results are compati- ble with the predominant genetic background of sponta- neous Rh phenotype splitting as investigated in an earlier
study.4 In the vast majority of individuals with mixed RhD and RhC or RhE phenotype, myeloid-lineage restricted mosaicism caused by LOH of variable chromosome 1 stretches encompassing the RHD/RHCE loci had been identified. In the present study, for the first time, this genetic background was documented with respect to spontaneous Rhc phenotype anomaly.
In contrast, proposita A showed a different spectrum of tissue involvement by LOH. Besides some of the myeloid stem cells and BFU-E colonies, also lymphocytes and hair roots were affected by this somatic change. These results indicate that LOH developed in a pluripotent stem cell line at an early stage of ontogenetic development, still capable of differentiating into hematopoietic as well as hair root cells. Such a constellation has not so far been described.
Copy-neutral LOH on 1p can compromise expression of many different genes, including those encoding Rh blood group antigens. The analysis of discrepant blood grouping
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haematologica | 2019; 104(3)