This thesis describes the synthesis of oligonucleotide conjugates by means of the strain induced [2+3] dipolar cycloaddition is described. To this end, dibenzocyclooctyne containing phosphoramidite... Show moreThis thesis describes the synthesis of oligonucleotide conjugates by means of the strain induced [2+3] dipolar cycloaddition is described. To this end, dibenzocyclooctyne containing phosphoramidite building blocks were synthesized. These building blocks were subsequently used in the solid phase synthesis of RNA and DNA oligonucleotides yielding dibenzocyclooctyne containing oligonucleotides. These oligonucleotides were used in strain induced cycloadditions with a variety of azides e.g. fluorescent labels, oligosaccharides, oligopeptides and bovine serum albumin yielding the corresponding conjugates. Additionally, the synthesis of D-arabinose and D-ribose derived C-glycosides is described. These nucleoside derivatives were obtained from D-ribose and D-arabinose C-1 substituted hemi-ketals in BF3OEt2-triethyl silane mediated reductions. The results and mechanism regarding the stereoselectivity in these reductions are discussed. Show less
Versteegh, F.G.A.; Arkesteijn, S.G.J.; Bakker-Verweij, M.; Haanappel, K.; Delft, P. van; Phylipsen, M.; ... ; Harteveld, C.L. 2011
We report two novel alpha 2-globin gene mutations found in the same Surinamese family. The proband, a newborn presenting during neonatal screening with 21.3% Hb Bart's (gamma 4), proved to be a... Show moreWe report two novel alpha 2-globin gene mutations found in the same Surinamese family. The proband, a newborn presenting during neonatal screening with 21.3% Hb Bart's (gamma 4), proved to be a carrier of the common -alpha(3.7) deletion and a novel codon 32 (ATG>AGG) transversion that we named Hb Rotterdam. The father carried the same point mutation with borderline hemoglobin (Hb), MCV and low MCH values. The mother presented with a significant microcytic hypochromic anemia and also carried the -alpha(3.7) deletion and a second novel TAT>TAG transversion generating a stop codon at position 24. Shortly thereafter, Hb Rotterdam was again found in two unrelated adult females and in a Canadian newborn, all of African origin, suggesting that Hb Rotterdam could be a frequently occurring alpha(T) determinant in the Black population. Screening and characterization of the mutations, phenotype/genotype correlation and the issue of reporting newborn carriers of alpha-thalassemia (alpha-thal) are discussed. Show less
Kaufmann, J.O.; Harteveld, C.L.; Bakker-Verweij, M.; Arkesteijn, S.G.J.; Delft, P. van; Haak, H.; ... ; Giordano, P.C. 2010
During a second pilot study, intended to explore the possibility of a country wide implementation of carrier diagnostics for hemoglobinopathies in The Netherlands, we observed a new abnormal... Show moreDuring a second pilot study, intended to explore the possibility of a country wide implementation of carrier diagnostics for hemoglobinopathies in The Netherlands, we observed a new abnormal hemoglobin (Hb) variant in three members of a family of Scandinavian origin living in the Dutch city of The Hague (Den Haag). The proband, a 34-year-old female presented with low Hb, packed cell volume (PCV) and red blood cell (RBC) values but was normocytic and normochromic. High performance liquid chromatography (HPLC) analysis revealed a partially separated fraction following Hb A. Molecular diagnostics disclosed a TTT > TAT transversion at HBB:c.137 causing a Phe -> Tyr single amino acid substitution at position 45 of the beta-globin gene. Previously described heterozygous mutations at the same position [Hb Cheverly (Phe -> Ser) and Hb Arta (Phe -> Cys)] were reported to be associated with mild chronic hemolysis similar to this case. We describe the hematological features of the six family members, the biochemical and molecular data and we discuss the possible consequences in combination with the common beta-thalassemia (beta-thal) trait. Show less
Kaufmann, J.O.; Phylipsen, M.; Neven, C.; Huisman, W.; Delft, P. van; Bakker-Verweij, M.; ... ; Giordano, P.C. 2010
We report two new abnormal hemoglobins (Hbs) caused by mutations on the alpha 2 gene. One resulted into an Asn-->His substitution at position 68, the other in a Leu-->Gln substitution at... Show moreWe report two new abnormal hemoglobins (Hbs) caused by mutations on the alpha 2 gene. One resulted into an Asn-->His substitution at position 68, the other in a Leu-->Gln substitution at position 125. The first mutation was observed in a 61-year-old North European Belgian male during Hb A(1c) analysis and subsequently in other members of his family. The variant was expressed at a normal level and caused no hematological abnormalities in the carriers. The second was found in a 27-year-old Turkish male living in The Hague, The Netherlands, who presented with microcytic hypochromic parameters without iron deficiency and was also carrier of the common alpha 2 IVS-I (-5 nt) deletion. Show less
We report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions... Show moreWe report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions masked by Hb E [beta 26(B8)Glu -> 4Lys] in the homozygous state. The second had an unusual Hb H disease caused by compound heterozygosity for two different alpha 2 polyadenylation site mutations masked by a beta-thalassaemia heterozygosity. The third had an intermediate alpha-thalassaemia with considerable anaemia caused by an as yet unknown polyadenylation site (AATAAA>AATAAC) mutation in combination with a common RW deletion masked by a common Hb C [beta 6(A3)Glu -> Lys] heterozygosity. Diagnostic methods, genotype/phenotype correlations and the chance of overlooking these combinations during risk assessment in a multiethnic society are discussed. Show less
![Hb BOSKOOP [HBA2c.112C > T p.Pro38Ser]: A NEW alpha 2 CHAIN VARIANT OBSERVED IN A MORROCAN FAMILY](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=4a628fe0793c982a057a&solr_nav%5Bpage%5D=0&solr_nav%5Boffset%5D=3)
![Hb Den Haag [beta 45(CD4)Phe -> Tyr]. A New Hemoglobin Variant Observed During Early Pregnancy Diagnostics](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=4a628fe0793c982a057a&solr_nav%5Bpage%5D=0&solr_nav%5Boffset%5D=5)
![Hb St. TRUIDEN [alpha 68(E17)Asn -> His] AND Hb WESTEINDE [alpha 125(H8)Leu -> Gln]: TWO NEW ABNORMALITIES OF THE alpha 2-GLOBIN GENE](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=4a628fe0793c982a057a&solr_nav%5Bpage%5D=0&solr_nav%5Boffset%5D=6)
