Weak D caused by a founder deletion in the RHD gene

Abstract

The currently reported deletion was derived from a common founder. This deletion appears to represent not only the first large deletion associated with weak D but also the weakest of weak D alleles so far reported. This highly unusual genotype-phenotype relationship may be attributable to the additive effect of three distinct mechanisms that affect mRNA formation, mRNA stability, and RhD/ankyrin-R interaction, respectively.

A DEL phenotype attributed to RHD Exon 9 sequence deletion: slipped‐strand mispairing and blood group polymorphisms

“…DNA repair enzymes remove these loops resulting in a shorter DNA structure. Schematic diagram for SSM adapted from Levinson and Gutman and Fichou et al The TMEM50A gene is previously known as SMP1 gene.…”

“…Finally, SSM has been implicated in generating other RhD polymorphisms . Andrews and coworkers reported a 4‐bp deletion in a variant RHD gene, RHD*01N.13 ( RHD*487_490delACAG ), bordered by STR resulting in a D– phenotype although no genetic mechanism was put forward at the time.…”

“…Flegel and coworkers pointed to SSM as a possible mutation mechanism causing triplet deletion after observing repeat sequences for partial RH variants RHD*DVL‐1 , RHD*DVL‐2, and RHCE*ceBP . Fichou and coworkers described a role for SSM when suggesting genetic mechanisms that resulted in a weak D phenotype due to a deletion that spanned across RHD Exon 10.…”

“…AET 5adsorption and elution technique; -5 negative reaction; (1) 5 weakly positive; 1 to 11 5 positive reaction. 33 The TMEM50A gene is previously known as SMP1 gene. Table 2.…”

Molecular basis of weak D expression in the Indian population and report of a novel, predominant variant RHD allele

“…To the best of our knowledge duplications involving several kilobases of the RHD gene have never been reported before and only very few large deletions have been documented: whole RHD gene deletion, RHD(delEx8), and RHD(delEx10). 4,[23][24][25] Duplications are much more complicated to identify and to characterize than deletions as a quantitative analysis method is required. So far only two approaches have been developed and have proven their efficiency for such an application: our QMPSF approach and a MLPA-based system.…”