Some null or mod phenotypes are caused by mutations in genes other than the blood group gene. Rhnull, the very rare null phenotype of the Rh system, has two main modes of inheritance. The rare recessive ‘amorph’ type arises from homozygosity for a deletion of RHD (as seen in most D-negatives) together with homozygosity for RHCE containing inactivating mutations (Huang et al. ; Chérif-Zahar et al. ). Consequently, neither Rh protein is produced. The less rare ‘regulator’ type of Rhnull, which was known for many years from family evidence to be inherited as a rare recessive inhibitor gene at a locus independent of the Rh genes, results from homozygosity for inactivating mutations in RHAG, the gene encoding the RhAG, which probably forms heterotrimers with the Rh proteins (Fig. ) and appears to be essential for expression of the Rh antigens on the Rh proteins (Cherif-Zahar et al. ). In addition to absence of expression of Rh antigens in Rhnull, there are no antigens of the LW blood group system (ICAM4) and reduced expression of glycophorin B and CD47, all of which appear to be part of a membrane protein complex. Rhnull red cells are stomatocytic and most individuals with Rhnull have a compensated haemolytic anaemia, which may be severe enough to merit splenectomy. Homozygosity for missense mutations in RHAG may cause reduced expression of RhAG and of Rh antigens (Rhmod phenotype) (Cherif-Zahar et al. ), in addition to the presence of a low frequency antigen on RhAG (Tilley et al. ).
Foreword, vii Preface to the third edition, viii Some abbreviations used, ix 1 Human blood groups: introduction, 1 2 ABO, H, and Lewis systems, 11 3 MNS blood group system, 96 4 P1PK, Globoside, and FORS blood group systems, plus some other related blood groups, 162 5 Rh and RHAG blood group systems, 182 6 Lutheran blood group system, 259 7 Kell and Kx blood group systems, 278 8 Duffy blood group system, 306 9 Kidd blood group system, 325 10 Diego blood group system, 336 11 Yt blood group system, 354 12 Xg blood group system, 359 13 Scianna blood group system, 371 14 Dombrock blood group system, 376 15 Colton blood group system, 384 16 LW blood group system, 391 17 Chido/Rodgers blood group system, 400 18 Gerbich blood group system, 410 19 Cromer blood group system, 427 20 Knops blood group system and the Cost antigens, 439 21 Indian blood group system and the AnWj antigen, 449 22 Ok blood group system, 457 23 Raph blood group system, 461 24 JMH blood group system, 465 25 I and i antigens, and cold agglutination, 469 26 Gill blood group system, 485 27 Junior and Langereis blood group systems, 487 28 Er antigens, 493 29 Low frequency antigens, 495 30 High frequency antigens, including Vel, 500 31 Sid antigen, 505 32 HLA (Human Leucocyte-Associated) Class I antigens on red cells, 512 33 Polyagglutination and cryptantigens, 515 Index, 524