Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
Transfus Med Hemother ; 50(1): 51-65, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36818776

RESUMO

Background: The blood supply for patients with foreign ethnic backgrounds can be challenging, as they often have blood group and HPA patterns that differ from the variants prevalent in the German population. In addition, hemoglobinopathies requiring regular blood transfusion may be more common in such populations. High-throughput genotyping tests can facilitate the identification of the most compatible blood products, thereby reducing the risk of transfusion reactions. The present study reports the results of a molecular study for the Kidd (JK) blood group. Allele frequencies and antigen prevalence data are presented for >8,000 individuals of various origins. Material and Methods: More than 8,000 blood donors were genotyped for 22 blood group systems and 5 HPA genes using an amplicon-based next-generation sequencing (NGS) approach. As part of the test system, we focused on the JK system in more detail. Double-ARMS PCR analysis was performed for the haplotype phasing of the JK1/JK2 and two more common synonymous polymorphisms. We performed transcript analysis to detect potential alternative splice products. For a subset of samples, a comparison between serotype and red cell genotype was conducted. Allele frequencies were determined for geographically different panels of individuals. Results: We successfully genotyped the JK blood group for 99.6% of the samples. Haplotype phasing revealed 96 different alleles. For several alleles that carry one of the synonymous SNVs c.588A>G and c.810G>A, we could not confirm the reported JK phenotypes. We found a higher frequency of JK:1 alleles for all populations except Iraqis. JK*01W.01 alleles were more common in the Asian groups and sub-Saharan Africans. A variant of the allele JK*02N.01 was present exclusively in Southeast Asians. Conclusion: Genotyping for JK antigens with a targeted NGS assay can easily be performed in routine. The interpretation that c.588A>G leads to a weak phenotype and c.810G>A to a null phenotype is questionable. IDs as well as the descriptions of alleles carrying these SNVs should be revised in the ISBT JK table.

2.
Transfus Med Hemother ; 47(5): 396-408, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33173458

RESUMO

BACKGROUND AND AIMS: Only little is known about blood groups other than ABO blood groups and Rhesus factors in Arabian countries and Iran. During the last years, increased migration to Central Europe has put a focus on the question how to guarantee blood supply for patients from these countries, particularly because hemoglobinopathies with the need of regular blood support are more frequent in patients from that region. Therefore, blood group allele frequencies should be determined in individuals from Arabian countries and Iran by molecular typing and compared to a German rare donor panel. METHODS: 1,111 samples including 800 individuals from Syria, 147 from Iran, 123 from the Arabian Peninsula, and 41 from Northern African countries were included in a MALDI-TOF MS assay to detect polymorphisms coding for Kk, Fy(a/b), Fynull, Cw, Jk(a/b), Jo(a+/a-), Lu(a/b), Lu(8/14), Ss, Do(a/b), Co(a/b), In(a/b), Js(a/b), Kp(a/b), and variant alleles RHCE*c.697C>G and RHCE *c.733C>G. Yt(a/b), S-s-U-, Velnull, Conull, and RHCE *c.667G>T were tested by PCR-SSP. RESULTS: Of the Arabian donors, 2% were homozygous for the FY *02.01N allele (Fynull), and 15.7% carried the heterozygous mutation. However, 0.8% of the German donors also carried 1 copy of the allele. 3.6% of all and 29.3% of Northern African donors were heterozygous for the RHCE *c.733C>G substitution, 0.4% of the Syrian probands were heterozygous for DO *01/DO *01.-05, a genotype that was lacking in German donors. Whereas the KEL *02.06 allele coding for the Js(a) phenotype was missing in Germans; 0.8% of the Syrian donors carried 1 copy of this allele. 1.8% of the Syrian but only 0.3% of the German donors were negative for YT *01. One donor from Northern Africa homo-zygously carried the GYPB *270+5g>t mutation, inducing the S-s-U+w phenotype, and in 2 German donors a GYPB *c.161G>A exchange, which induces the Mit+ phenotype, caused a GYPB *03 allele dropout in the MALDI assay. The overall failure rate of the Arabian panel was 0.4%. CONCLUSIONS: Some blood group alleles that are largely lacking in Europeans but had been described in African individuals are present in Arabian populations at a somewhat lower frequency. In single cases, it could be challenging to provide immunized Arabian patients with compatible blood.

3.
Transfus Med Hemother ; 47(4): 326-336, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32884505

RESUMO

The U antigen (MNS5) is one of 49 antigens belonging to the MNS blood group system (ISBT002) carried on glycophorins A (GPA) and B (GPB). U is present on the red blood cells in almost all Europeans and Asians but absent in approximately 1.0% of Black Africans. U negativity coincides with negativity for S (MNS3) and s (MNS4) on GPB, thus be called S-s-U-, and is thought to arise from homozygous deletion of GYPB. Little is known about the molecular background of these deletions. Bioinformatic analysis of the 1000 Genomes Project data revealed several candidate regions with apparent deletions in GYPB. Highly specific Gap-PCRs, only resulting in positive amplification from DNAs with deletions present, allowed for the exact genetic localization of 3 different breakpoints; 110.24- and 103.26-kb deletions were proven to be the most frequent in Black Americans and Africans. Among 157 CEPH DNAs, deletions in 6 out of 8 African ethnicities were present. Allele frequencies of the deletions within African ethnicities varied greatly and reached a cumulative 23.3% among the Mbuti Pygmy people from the Congo. Similar observations were made for U+var alleles, known to cause strongly reduced GPB expression. The 110- and 103-kb deletional GYPB haplotypes were found to represent the most prevalent hereditary factors causative of the MNS blood group phenotype S-s-U-. Respective GYPB deletions are now accessible by molecular detection of homo- and hemizygous transmission.

5.
Transfusion ; 48(9): 1898-905, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18513251

RESUMO

BACKGROUND: Little is known about the mechanism by which amino acid polymorphisms outside the catalytically active cleft of ABO glycosyltransferases cause weak ABO phenotypes. STUDY DESIGN AND METHODS: Extensive ABO phenotyping and genotyping were performed to classify the blood of a healthy blood group O donor with weak isoagglutinins. ABO antigen and glycosyltransferase expression profiles were then studied in eukaryotic transfection experiments, and the topology of ABO glycosyltransferase was analyzed. RESULTS: The donor's red blood cells were retyped as A(weak), and his serum contained weakly reactive anti-A and anti-B. Sequence analysis revealed two novel ABO alleles. A donor splice-site mutation detected at the exon 6/intron 6 junction of an ABO*A101 allele was predicted to result in skipping exon 6 in the mRNA. The other haplotype displayed a single 688G>C substitution predicting a Gly230Arg exchange in the catalytic domain in an otherwise normal ABO*B101 allele. The transfection studies revealed very weak expression of B antigen by the novel ABO*B allele. According to the topologic analysis, steric hindrance due to the Gly230Arg exchange may cause conformational changes in the variant B transferase. Compared to the wild-type B transferase, the transfected cells exhibited lower-level protein expression and intracellular dislocation. CONCLUSION: This study provides first evidence that aberrant trafficking of variant ABO transferases may be involved in the formation of weak ABO phenotypes.


Assuntos
Glicosiltransferases/genética , Polimorfismo Genético , Sistema ABO de Grupos Sanguíneos/genética , Sistema ABO de Grupos Sanguíneos/imunologia , Alelos , Linhagem Celular Tumoral , Citometria de Fluxo , Genótipo , Glicosiltransferases/metabolismo , Células HeLa , Humanos , Espaço Intracelular/metabolismo , Microscopia de Fluorescência , Mutação , Transporte Proteico , Transfecção
6.
Blood Transfus ; 12(1): 73-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24333057

RESUMO

BACKGROUND: The Colton blood group antigens Co(a), Co(b) and Co3 are encoded by the AQP1 gene which produces a water channel forming integral protein. The extremely rare Co-deficiency enables immunisation against the Co3 isoantigen. MATERIALS AND METHODS: Four patients from different regions of Europe who belong to the ethnic minority of Romani (Gypsy) presented with irregular antibodies against a high frequency red blood cell antigen. Positive cross-matches with all red blood cells tested were reported. An Anti-Co3 antibody was identified as the cause of incompatibility in the four cases. The genetic background was determined by polymerase chain reaction typing with sequence-specific primers and by DNA sequencing. RESULTS: The Co(a-b-) phenotype was confirmed in the four patients despite the fact that genotyping revealed the CO*01 allele of the AQP1 gene. A homozygous AQP1 c.601delG mutation, leading to a frame shift and producing a premature stop in the next codon, was responsible for the Co-negative phenotype in all four cases. While one patient was successfully transfused with blood from his sibling with the identical mutation, another case, a baby affected by haemolytic disease of the newborn, recovered without transfusion. DISCUSSION: Despite the difficulties in undertaking a population study to determine the prevalence of this AQP1 c.601delG allele in the ethnic minority of Romani, the observations described in this report clearly suggest an accumulation of this mutation, which causes the Co(a-b-) phenotype, in Romani (Gypsy) patients. Further studies are necessary to prove such an accumulation.


Assuntos
Aquaporina 1/genética , Sequência de Bases , Antígenos de Grupos Sanguíneos/genética , Roma (Grupo Étnico)/genética , Deleção de Sequência , Adulto , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Saudi J Anaesth ; 5(1): 101-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21655031

RESUMO

We report on a patient with acute intermittent porphyria, who received 8 AB0 incompatible units of packed red blood cells in an emergency situation. She never showed any signs of severe intravascular haemolysis. The patient died after four weeks because of a multi-organ failure caused from the malpractice of the porphyria. The problems of bedside testing, mixing field reaction, fresh frozen plasma and molecular-genetic determination of bloodgroup were discussed.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA