RhD variant caused by an in-frame triplet duplication in the RHD gene

Authors

  • Janet C. Pereira,

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Maria J. Rodrigues,

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Louise Tilley,

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Joyce Poole,

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Teresa Chabert,

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Maria L. Ribeiro

    1. From the Unidade Hematologia Molecular, Departamento Hematologia, Centro Hospitalar Coimbra, EPE, Coimbra, Portugal; the Centro Regional de Sangue de Lisboa, Instituto Português do Sangue, I.P. Lisbon, Portugal; and BITS/IBGRL, Bristol, UK.
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  • Supported in part by grant from FCT and FSE in the scope of the III Communitarian Board of Support, POCTI—Formar e Qualificar—Medida 1.1, Portugal (PRAXIS XXI/BD/11223/97).

Janet Pereira, Unidade Hematologia Molecular, Hospital Pediátrico Coimbra, Avenida Bissaya Barreto, 3000-076 Coimbra, Portugal; e-mail: uhm@chc.min-saude.pt.

Abstract

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.

STUDY DESIGN AND 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.

CONCLUSION: 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.

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