RhD variant caused by an in-frame triplet duplication in the RHD gene.
BACKGROUND
The RHD gene is highly polymorphic and a large number of D variants have already been detected. Several mechanisms are involved in the origin of D variants. In-frame deletions, resulting in a single-amino-acid deletion, have been described associated with RhD and RhCE variants. No in-frame duplications and/or insertions have been reported in the RH genes to date.


METHODS
Blood samples from a Brazilian blood donor and his sister were serologically tested with routine anti-D reagents and anti-D panels (ALBAclone advanced partial D typing kit, Alba Bioscience Limited; and D-Screen, Diagast), followed by molecular biology techniques, RHD polymerase chain reaction with sequence-specific priming and sequencing.


RESULTS
Samples tested negative with routine immunoglobulin M (IgM) anti-D reagents and positive with IgG anti-D, which detect weak D cells. The pattern of results with anti-D panels did not correspond to any described before. A 3-bp in-frame duplication within Exon 1 (c.75_77dupTCT), resulting in the duplication of leucine 26 (p.Leu26dup), was identified in the two samples.


CONCLUSIONS
We report the first RhD variant associated with a 3-bp in-frame duplication in the RHD gene, predicted to be located within the RhD protein transmembrane domain that might be expected to result in a weak-D-like phenotype, concordant with serologic findings.
Pereira
Janet C
JC
Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal.
Rodrigues
Maria J
MJ
Tilley
Louise
L
Poole
Joyce
J
Chabert
Teresa
T
Ribeiro
Maria L
ML
D005091:Exons; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D012204:Rh-Hr Blood-Group System / Q000235:genetics* / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen