Molecular Defects of the RHCE Gene in Rh-Deficient
Individuals of the Amorph Type
Baya Chérif-Zahar,
Giorgio Matassi,
Virginie Raynal,
Pierre Gane,
Wolfgang Mempel,
Carmen Perez, and
Jean-Pierre Cartron
From INSERM U76, Institut National de la Transfusion Sanguine, Paris,
France; the Ludwig Maximilians Universität München,
Medizinische Klinik und Poliklinik III, München, Germany; and the
Servicio de Haematologia, Hospital San Agustin, Linares, Spain.
The deficiency of Rh proteins on the red blood cells from
individuals of the Rhnull amorph type may be the result of
homozygosity for a silent allele at the RH locus. This phenotype is
also associated with the lack or reduced expression of glycoproteins
(Rh50, CD47, LW, and glycophorin B), which interact with Rh
polypeptides to form the multisubunit Rh membrane complex. In this
study, we describe two molecular alterations affecting the RHCE
gene in two unrelated Rhnull amorph individuals bearing
Rh50 and CD47 normal transcripts. The first type of mutation, located
at the donor splice-site in intron 4, induced the activation of two
cryptic splice-sites within this intron and one such site in exon 4 that all generated aberrant transcripts. The second type of mutation
affected the coding region and introduced a frameshift and a premature
stop codon resulting in a shorter predicted protein (398 v 417 residues), including a completely different C-terminus of 76 amino
acids. This suggests that protein folding and/or
protein-protein interaction mediated by the C-terminal domain of the Rh
proteins may play a role in the routing and/or stability of the
Rh membrane complex.
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 639-646
© 1998 by the American Society of Hematology.
