Rhnull is a syndrome serologically characterized by
the
deficiency of all Rh antigens on human red
blood cells. Rhnull is divided into two types: regulator and
amorph. Recently, Cherif-Zahar et al.
proposed that the RHAG gene encoding the Rh50 glycoprotein is
a candidate for inducing regulator
type Rhnull. We investigated both the RH and RHAG
genes in an Rhnull individual. The reticulocytes
from the propositus had RHD, RHcE, and RHCe
transcripts without any mutation. However, the
sequence analysis of RHAG cDNA showed a deletion of 122 bp from
nucleotide 946 to 1067. This
deletion was revealed to be due to a homozygous splicing mutation, which
is a single base
substitution at the consensus sequence of the splicing acceptor site
(AG→AT). The mutation
appeared to break the ‘GT-AG’ splicing rule and to cause
122 bp exon skipping accompanied by a
frameshift. This study confirms that the RHAG gene is the
most likely candidate for the ‘regulator’
gene of Rhnull cases.