Small deletions within the RHD coding sequence: a report of two novel mutational events and a survey of the underlying pathophysiologic mechanisms. Issue 1 (21st May 2012)

• Record Type: Journal Article
• Authors: Chen, Jian‐Min; Fichou, Yann; Jamet, Déborah; Dupont, Isabelle; Cooper, David N.; Le Maréchal, Cédric; Férec, Claude
• Is Part Of: Transfusion. Volume 53:Issue 1(2013)
• Page Start: 206
• Page End: 210
• Publication Date: 2012-05-21
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/j.1537-2995.2012.03713.x
• Languages: English
• ISSNs: 0041-1132

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>BACKGROUND:</bold> Some 270 variants in the <italic>RHD</italic> gene have so far been identified. Of these, approximately 6% (n = 17) are small (≤20 bp) deletions occurring within the gene's coding sequence. Fourteen of these small deletions disrupted the reading frame of the <italic>RHD</italic> gene, resulting almost invariably in a D– phenotype.</p> <p> <bold>STUDY DESIGN AND METHODS:</bold> Two subjects who displayed D phenotype ambiguity or a genotype‐phenotype discrepancy were referred to our laboratory for <italic>RHD</italic> genetic analysis. Hemizygosity for the most common 70‐kb <italic>RHD</italic> deletion was first determined in both subjects by long‐range polymerase chain reaction (PCR) followed by PCR amplification and sequencing of all 10 exons of the <italic>RHD</italic> gene in the nondeleted allele individually.</p> <p> <bold>RESULTS:</bold> Two novel lesions in the <italic>RHD</italic> gene were identified on the nondeleted alleles, a 14‐bp frameshifting deletion within Exon 1 (i.e., c.29_42delGGCGCTGCCTGCCC) and an 11‐bp frameshifting deletion within Exon 3 (i.e., c.361_371delTTGTCGGTGCT), in Subjects 1 and 2, respectively.</p> <p> <bold>CONCLUSION:</bold> By reference to previously reported small deletions in the <italic>RHD</italic> gene, the 11‐bp deletion in Exon 3 may be safely regarded as a bona fide D– variant. Although the association of the 14‐bp deletion in Exon 1 with a weak D phenotype appears to be genuine, the underlying molecular mechanism still remains to be clarified. Evaluation of all known small <italic>RHD</italic> deletions points to slippage mutagenesis as the major underlying mutational mechanism. [Correction statement added after online publication 21‐May2012: The spelling of bona has been updated.]</p> </abstract>