Molecular structures identified in serologically <scp>D</scp>– samples of an admixed population

Boggione, Carolina Trucco; Brajovich, Melina Eliana Luján; Tarragó, Marcel; Mattaloni, Stella Maris; Biondi, Claudia; Muñiz‐Díaz, Eduardo; Nogués, Núria; Cotorruelo, Carlos

doi:10.1111/trf.12691

Cited by 10 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of the inclusion of more than two exons in the suggested algorithm, it was necessary to carry out complementary studies to characterize RHD -positive / D-negative individuals. In the Argentinean population, approximately 2% of D-negative individuals harbor an RHD allele [25,26]. This information has been recently corroborated in a study by Trucco Boggione et al [18] and in our results, supporting that the assessment of noninvasive prenatal RHD using exon 5 and 10 is capable to appropriately predict fetal phenotype and guide target antenatal prophylaxis.…”

Section: Discussionsupporting

confidence: 76%

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

Blanco

Giacomi²,

Slobodianiuk³

et al. 2018

Transfus Med Hemother

View full text Add to dashboard Cite

Introduction: Since anti-D immunoprophylaxis given to D-negative pregnant women is a blood product, blood donations have an impact on the availability of prophylactic doses. The Pan American Health Organization reported, in June 2017, that less than half of blood donors are volunteers in Latin America and the Caribbean. In these countries, guidelines for use of anti-D prophylaxis are still controversial. The aim of this study was to demonstrate the convenience of a simple and cost-effectivene non-invasive prenatal diagnostic assay for anti-D prophylaxis optimization in multiethnic populations. Methods: Cell-free fetal DNA from plasma samples of D-negative pregnant women were analyzed by real-time PCR for simultaneous amplification of sequences of exons 5 and 10 of the RHD gene. Fetal RHD genotype was determined in 111 pregnant women. Neonates' phenotype was determined 72 h after birth. Results: Genotyping predicted fetal phenotype with 100% accuracy. Prenatal diagnosis showed 78% RHD-positive and 22% RHD-negative neonates. Conclusion: We demonstrated that, beyond the large genetic variation of the Rh system and the numerous D variants present in multiethnic groups, non-invasive fetal RHD genotyping using two sequences of the gene can be enough for clinical application in an admixed population. This robust technique of simple implementation allows to determine fetal RHD in maternal blood with high sensitivity, specificity, and accuracy. The introduction of fetal RhD genotyping as part of an antenatal screening program constitutes a reliable manner to optimize anti-D prophylaxis; however, it has not been implemented so far in most American countries.

show abstract

Section: Discussionsupporting

confidence: 76%

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

Blanco

Giacomi²,

Slobodianiuk³

et al. 2018

Transfus Med Hemother

View full text Add to dashboard Cite

show abstract

“…Although the main RHD alleles resulting in a D- phenotype, i.e. RHDΨ and (C)ce s , are most frequently cis -associated with RHCE*ce , other RHD gene variants in D- individuals, including several hybrid genes, have been shown to segregate with RHCE alleles expressing C and/or E (C/E+) antigens in Caucasian, Asian, African, and mixed populations [4,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. …”

Section: Introductionmentioning

confidence: 99%

RHD-Positive Alleles among D- C/E+ Individuals from India

Kulkarni

Gogri

Parchure

et al. 2018

Transfus Med Hemother

View full text Add to dashboard Cite

Background: Molecular bases of blood group systems, including Rh blood group, have been poorly studied in the Indian population so far, while specificities of Europeans, East Asians and Africans have been well known for years. In order to gain insights into the molecular bases of this population, we sought to characterize the RHD allele in D- Indian donors expressing C and/or E antigen(s). Methods:RHD gene was analyzed in 171 serologically D-, C/E+ samples by standard molecular methods such as quantitative, multiplex PCR of short fluorescent fragments (QMPSF) and direct sequencing when necessary. Results:RHD whole gene deletion at the homozygous state was found to be the most common genotype associated with D- phenotype (118/171, 69.0%). Nonfunctional, negative hybrid genes with reported molecular backgrounds were observed in approximately one-third of the samples, while only four samples carry single-nucleotide variations, including one novel nonsense (RHD(Y243X)), one novel frameshift (RHD(c.701delG)), and two missense (RHD(T148R) and RHD(T148R, T195M)) alleles. Conclusion: Overall we report for the first time the molecular bases of D antigen negativity in the D-, C/E+ Indian population, which appears to be qualitatively similar to other populations, but with a population-specific, quantitative distribution of D-- alleles.

show abstract

“…To note, RHD*01N.75 (c.581insG) and RHD*DEL43 (c.46T>C) were the most prevalent variants found in D‐/ RHD + C/E+ donors following RHD*03N.01 (Table ), showing a higher frequency of these alleles in the population from Northwestern Argentina when compared with the central region . The null RHD*01N.75 variant, caused by a G insertion at position 581_582, is responsible for a premature stop codon at the 198 nucleotide of the mRNA, generating a truncated protein with 197 amino acid residues resulting in a D negative phenotype.…”

Section: Resultsmentioning

confidence: 98%

“…The presence of RHD gene sequences was tested in all 526 D negative C and/or E positive samples by a multiplex PCR strategy as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Genetic and anthropological evidence showed that the Amerindian influence is higher in the Northwestern area than in other parts of Argentina . On the other hand, a high RHD allelic variability has been observed in the central area of the country . Taking together these findings and considering the clinical importance of altered D expression, the aim of this work was to investigate the molecular polymorphism within the RHD locus in individuals from the Northwestern region so as to develop a rational RHD genotyping strategy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of RHD locus polymorphism in D negative and D variant donors from Northwestern Argentina

et al. 2019

Self Cite

View full text Add to dashboard Cite

BACKGROUND A notable RHD variability has been observed in Central Argentina's current population attributed to the intermixing of different ethnic groups. The Northwestern region of the country is characterized by a markedly Amerindian genetic contribution. In this sense, the definition of the RHD polymorphism in individuals from this area was lacking. STUDY DESIGN AND METHODS A total of 757 donors from Northwestern Argentina, with D negative C and/or E positive (n = 526), and D variant (n = 231) phenotype defined by standard hemmaglutination tube techniques were genotyped using in‐house PCR strategies, commercial SNP arrays and Sanger sequencing. RESULTS Among D negative C and/or E positive samples, RHD null (15.40%) and DEL alleles (3.23%) were identified. One unreported SNP c.1001T>A responsible for a null allele was found. RHD*01N.75 (4.18%) and RHD*DEL43 (2.66%) were the most prevalent variants following RHD*03N.01 (8.75%). The characterization of serologic weak D phenotypes showed that RHD*weak D type 1, 2, and 3 variants were found only in 37.24% of the samples, whereas RHD*weak D type 93 was the most prevalent allele (25.11%). Also, a previously unreported missense variation c.764G>A was identified. CONCLUSIONS A RHD genotyping strategy for patients and donors from Northwestern Argentina must consider the detection of the frequently found RHD*01N.75, RHD*DEL43, and RHD*weak D type 93 variants. Taking into account that RHD*DEL43 has scarcely been found in North Americans and Europeans whereas RHD*01N.75 and RHD*weak D type 93 have never been described in populations other than Argentineans, these RHD variants could be attributed to Native Amerindian genetic influence.

show abstract

Molecular structures identified in serologically D– samples of an admixed population

Cited by 10 publications

References 28 publications

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

RHD-Positive Alleles among D- C/E+ Individuals from India

Characterization of RHD locus polymorphism in D negative and D variant donors from Northwestern Argentina

Contact Info

Product

Resources

About