Rhnull syndrome: identification of a novel mutation in RHce.
BACKGROUND
The deficiency of Rh proteins on red blood cells (RBCs) from individuals of the Rh(null) amorph type are the result of homozygosity for a silent RHCE in cis with a deleted RHD. A novel mutation in RHce was identified in two Caucasian Brazilian girls with the amorph type of Rh(null) who were born to parents who were first cousins.


METHODS
RBCs from the Rh(null) sisters and from family members were analyzed by serology and flow cytometry with specific antibodies. Genomic DNA and transcripts were tested by polymerase chain reaction and sequence analysis.


RESULTS
Rh(null) RBCs were nonreactive with anti-Rh and anti-LW. Molecular analyses showed a deletion of RHD and of one nucleotide (960/963; GGGG-->GGG) in exon 7 of the RHce. This deletion introduced a frameshift after Gly321, a new C-terminal sequence, and a premature stop codon, resulting in a shorter predicted protein with 357 amino acids.


CONCLUSIONS
The detection of a unique RHce transcript indicated that the two sisters were homozygous, whereas the other family members were heterozygous for the mutation. A novel mutation resulting in the amorph Rh(null) with loss of Rh antigen expression is described.
Rosa
K A
KA
Hemocentro Unicamp, Campinas, SP, Brazil.
Reid
M E
ME
Lomas-Francis
C
C
Powell
V I
VI
Costa
F F
FF
Stinghen
S T
ST
Watanabe
A M
AM
Carboni
E K
EK
Baldon
J P
JP
Jucksch
M M F
MM
Castilho
L
L
D000328:Adult; D001483:Base Sequence; D018388:Codon, Terminator; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006147:Guanine; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000235:genetics*; D013577:Syndrome; D014158:Transcription, Genetic
D018388:Codon, Terminator; C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D006147:Guanine