A new DEL variant caused by exon 8 deletion.
BACKGROUND
A 28-year-old woman of Lebanese origin experienced two stillbirths. At the time, serology typed her red blood cells as being group A D- and found an anti-D in her serum sample. Molecular biology analysis, however, showed that she was in fact RHD+.


METHODS
To better characterize this case, a full investigation including family members was undertaken. Classical serology techniques and DNA and RNA analysis were performed whenever possible.


RESULTS
Serology results showed that the patient's father and two brothers were D-. RHD genotyping demonstrated that her two brothers were indeed RHD+. Polymerase chain reaction (PCR) amplification was performed on each RHD 10 exons. Exon 8 did not amplify for the patient, her father, and her two brothers. Her mother and sister had exon 8. Messenger RNA analysis showed five RHD transcripts. The longest transcript was missing exon 8 but had a part of intron 7 inserted instead. Genomic DNA sequencing revealed a 995-bp deletion including part of intron 7, exon 8, and intron 8. This mutation, RHD(delEx8), was found to express a DEL in adsorption-elution. To facilitate the screening of this new DEL allele, a simple PCR-based assay was designed.


CONCLUSIONS
This novel allele represents the first observation of a large deletion at the genomic level within the RHD gene in Caucasian persons.
Richard
Martine
M
Héma-Québec, Research and Development, Quebec, Quebec, Canada.
Perreault
Josée
J
Constanzo-Yanez
Jessica
J
Khalifé
Samir
S
St-Louis
Maryse
M
D000328:Adult; D000906:Antibodies / Q000097:blood; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012204:Rh-Hr Blood-Group System / Q000235:genetics* / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid
D000906:Antibodies; D012333:RNA, Messenger; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen