Small deletions within the RHD coding sequence: a report of two novel mutational events and a survey of the underlying pathophysiologic mechanisms

Chen, Jian-Min, Fichou, Yann, Jamet, Déborah, Dupont, Isabelle, Cooper, David Neil ORCID: https://orcid.org/0000-0002-8943-8484, Le Maréchal, Cédric and Férec, Claude 2013. Small deletions within the RHD coding sequence: a report of two novel mutational events and a survey of the underlying pathophysiologic mechanisms. Transfusion 53 (1) , pp. 206-210. 10.1111/j.1537-2995.2012.03713.x

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Abstract

BACKGROUND: Some 270 variants in the RHD 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 RHD gene, resulting almost invariably in a D– phenotype. STUDY DESIGN AND METHODS: Two subjects who displayed D phenotype ambiguity or a genotype-phenotype discrepancy were referred to our laboratory for RHD genetic analysis. Hemizygosity for the most common 70-kb RHD 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 RHD gene in the nondeleted allele individually. RESULTS: Two novel lesions in the RHD 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. CONCLUSION: By reference to previously reported small deletions in the RHD 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 RHD deletions points to slippage mutagenesis as the major underlying mutational mechanism.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley
ISSN:	0041-1132
Last Modified:	24 Oct 2022 09:48
URI:	https://orca.cardiff.ac.uk/id/eprint/42203

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