Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2535-2540
Rh-Deficiency of the Regulator Type Caused by Splicing Mutations
in the Human RH50 Gene
Baya Chérif-Zahar,
Giorgio Matassi,
Virginie Raynal,
Pierre Gane,
Jean Delaunay,
Beatrix Arrizabalaga, and
Jean-Pierre Cartron
From INSERM U76, Institut National de la Transfusion Sanguine, Paris,
France; the Service d'Hématologie et INSERM U299, Hôpital
Kremlin Bicêtre, Le Kremlin Bicêtre, France; and the
Servicio Hematologia, Hospital de Cruces, Bilbao, Spain.
The Rh polypeptides and the glycoproteins Rh50, CD47, LW, and
glycophorin B, which interact in the red blood cell membrane to form a
multisubunit complex, are lacking or are severely reduced in the
Rh-deficiency syndrome. We previously reported that in several
Rhnull patients the RH50 gene was altered at the
coding sequence level, resulting in either a single amino acid
substitution or the synthesis of a truncated polypeptide. In the
present report, we have detected two mutations in the intronic region
of the RH50 gene that identify a new molecular mechanism
involved in Rh-deficiency. The first mutation affected the invariant G
residue of the 3
acceptor splice-site of intron 6, causing the
skipping of the downstream exon and the premature termination of
translation. The second mutation occurred at the first base of the
5 donor splice-site of intron 1. Both these mutations were found
in homozygote state. RNase protection assays demonstrated that the Rh50
mRNA level was strongly reduced or undetectable in the 3 and
5 splice mutants, respectively. The different mutations
affecting the RH50 gene are indicative of an heterogeneous
mutational pattern, which further supports the hypothesis that the lack
of the Rh50 protein may prevent the assembly or transport of the Rh
membrane complex to the red blood cell surface.
