Molecular genetic basis of the human Rhesus blood group system

Mouro, I; Colin, Yves; Chérif-Zahar, Baya; Cartron, JP; Kim, Caroline Le Van

doi:10.1038/ng0993-62

Cited by 272 publications

(150 citation statements)

References 24 publications

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“…30 The polymorphism of e and E antigens is associated with an SNP in exon 5 of RHCE (676G fi C) encoding an A226P substitution of the protein. 28 RHCE 676C is therefore used for PCR protocols for E. In both protocols used here, the forward amplification primer specifically detects RHCE 676C. Again, the main difference between the two protocols is that the amplicon size is smaller in method 2 than in method 1.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Gutensohn¹,

Müller

Thomann

et al. 2010

BJOG

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Objective The aim of the study was to determine the sensitivity, specificity and accuracy of noninvasive tests for the fetal rhesus CcEc (RHCE) alleles C, c and E in early pregnancy.Design A prospective clinical trial was carried out to evaluate diagnostic accuracy.Setting Women were recruited at four centres specialising in prenatal diagnosis. Peripheral blood and amniotic fluid samples were obtained and sent to a single laboratory for analysis.Sample A total of 233 tests (46 for C, 87 for c and 100 for E) were performed on 181 specimens obtained from pregnant women at weeks 12 to 28 (median week 16) of gestation.Methods Following automated extraction of fetal DNA from maternal plasma, two different real-time polymerase chain reaction (PCR) protocols were used for the detection of the C, c and E alleles of RHCE. The results of the PCR were compared with genotyping results for the amniotic fluid.Main outcome measures Failure rate, sensitivity, specificity and accuracy were the main outcome measures.Results Unequivocal results were obtained for all specimens. With the first PCR protocol, the sensitivity was 100% for C, 38% for c and 59% for E. In contrast, with the second protocol, the sensitivity for C, c and E was 100%. The specificity for all assays was found to be between 99% and 100%.Conclusions A highly accurate protocol has been identified for the detection of fetal RHCE alleles in maternal plasma in early pregnancy. This noninvasive approach can be considered as a useful test in the management of pregnancies with anti-c, anti-E or anti-C alloimmunisation.

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Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Gutensohn¹,

Müller

Thomann

et al. 2010

BJOG

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“…22 The availability of accurate noninvasive testing, for determination of fetal genotype could provide early first trimester testing for pregnant women with alloimmunisation that would eliminate the risk of the amniocentesis procedure-related pregnancy loss (up to 0.5%). Women whose fetus is determined to be negative for the specific antigen will continue with routine care.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive fetal RhCE genotyping from maternal blood

Geifman-Holtzman

Grotegut

Gaughan

et al. 2008

BJOG

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Background The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA.Objective To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used.Search strategy English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966Pubmed ( -2007, Ovid , CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation.Selection criteria A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded.Data collection and analysis From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy.Main results We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e.Conclusions The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

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“…The RhC/c epitope arises from a single base substitution within exon 2 at nt307, this substitution results in the incorporation of serine (RhC = CCT) or proline (Rhc = TCT) at amino acid 103 [6,12]. There are 5 additional base substitutions between the RHC and RHc alleles within exons 1 and 2; however, these polymorphisms have been shown not to be involved in the RhC/c serology [13,14].…”

Section: Introductionmentioning

confidence: 99%

Rh genotyping: Avoiding false‐negative and false‐positive results among individuals of African ancestry

2001

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High homology, variant alleles, and silent alleles have made the development of completely reliable genotyping assays for the RHD and RHC alleles difficult. An RHD pseudogene (RHD w) possessing a 37-bp insertion within exon 4 is common among serologically RhD-negative individuals of African descent and generates false-positive results in previously reported RhD genotyping assays. Genotyping RhC is problematic due to exon 2 homology between RHD and RHC; however, an RHC-specific 109-bp insertion within intron 2 has been reported useful for genotyping. Primers flanking the exon 4 insertion point were used for detection of RHD and RHD w among a total of 231 serotyped individuals: 134 African American, 85 Caucasian, and 12 RhD serotype-negative/genotype-positive, D-sensitized women. Primers flanking the RHC-specific intron 2 insertion were used to genotype 282 serotyped individuals (128 African American, 154 Caucasian) and were compared to RHC genotyping using the exon 1 RhC-specific nt48 cytosine polymorphism. Complete correlation was observed between genotyping with the RHD w primer pair and serotyping among 219 individuals and 10/12 previous RHD false-positive genotyping results were resolved. RHD w was detected in 19% (n = 4/21) of RhD seronegative African Americans and 4.4% (n = 5/113) of RhD seropositive African Americans. When using the 109-bp intron 2 insertion for genotyping of RHC, a 23.9% (n = 11/46) false-negative rate was observed among African American RhCc serotyped heterozygotes. Utilization of the exon 1 nt48 cytosine for indirect genotyping of RHC yielded a 7.2% (n = 4/55) and 56.3% (n = 45/80) false-positive rate among Rhcc Caucasians and African Americans, respectively. We conclude that these additional reactions, though not sufficient alone, can be useful supplements to existing Rh genotyping assays. Am.

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Molecular genetic basis of the human Rhesus blood group system

Cited by 272 publications

References 24 publications

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Noninvasive fetal RhCE genotyping from maternal blood

Rh genotyping: Avoiding false‐negative and false‐positive results among individuals of African ancestry

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