33 research outputs found
Association of α globin gene quadruplication and heterozygous β thalassemia in patients with thalassemia intermedia
No full textTen patients with thalassemia intermedia with variable
severity and apparent simple heterozygosis for b0 39 C>T
nonsense mutation were submitted to clinical, hematologic
and molecular studies. The presence of an unknown
molecular defect (silent b-thalassemia) unlinked to the b
cluster interacting with the heterozygous b thalassemia,
was previously postulated in these families. Analysis of the
a globin gene cluster with PCR-based methods (MLPA,
GAP-PCR, digestion with restriction enzymes) detected
complex rearrangements in the a cluster. A duplication of
the a globin gene locus, including the upstream regulatory
region, was present in all the patients, associated in some
of them with deletion or non-deletion a thalassemia. The
variability of the clinical phenotype correlates with the
degree of the globin chain imbalance. The presence of a
globin cluster duplication should be considered in patients
heterozygote for b-thalassemia with thalassemia intermedia
phenotype and in the carriers of suspected silent b thalassemia.
Key words: thalassemia intermedia, a-globin gene quadruplication,
silent b thalassemia, MLPA.
Citation: Sollaino MC, Paglietti ME, Perseu L, Giagu N, Loi D,
and Galanello R. Association of a globin gene quadruplication
and heterozygous b thalassemia in patients with thalassemia
intermedia. Haematologica 2009.94:1445-1448.
doi: 10.3324/haematol.2009.005728
©2009 Ferrata Storti Foundation. This is an open-access paper
Limits to the use of the glucose 6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase index for the detection of glucose 6-phosphate dehydrogenase deficiency
No full textA new β chain hemoglobin variant with increased oxygen affinity: Hb Santa Giusta Sardegna [β93(F9)Cys→Trp; HBB c.282T>G]
No full textDuring a screening program for the identification of β-thalassemia (β-thal) carriers in Sardinia, Italy, we identified two subjects with increased hemoglobin (Hb) levels and an abnormal Hb variant. The same variant was detected in a family member. DNA sequencing revealed a TGT > TGG mutation at codon 93 of the β-globin gene. Structural analysis demonstrated that the cystine residue at position 93 of the β chain was substituted by tryptophan. Since this amino acid substitution had not yet been reported, we designated this variant Hb Santa Giusta Sardegna for the place of birth of the subjects. This amino acid substitution occurs at the tyrosine pocket of the β chain as well as at the α1β2/α2β1 contact of the quaternary structure of the molecule. The presence of this Hb in the hemolysate causes an increased oxygen affinity, a slightly reduced Bohr effect and a reduced heme-heme interaction (n50, Hill's constant) in comparison with those of Hb A
Simultaneous Automated Determination of Glucose 6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase Activities in Whole Blood
No full textPeer Reviewe
α-globin gene quadruplication and heterozygous β-thalassemia: a not so rare cause of thalassemia intermedia
No full textThe association of alfa-gene quadruplication and heterozygous beta-thalassemia has been recognized in individuals and families whose thalassemia intermedia has previously been attributed to the interaction of heterozygous beta-thalassemia and an unknown melecular defect unlinked to the beta-cluster. The MLPA method was applied and revealed an extended duplication on the alfa-cluster in 19 of them
Structure-function relationship in a variant haemoglobin: a combined computational-experimental approach
No full textOur study examines the functional and structural effects of amino acid substitution in the distal side of b-chains of human Hb Duarte (a b62Ala/Pro). We have compared the functional properties of the purified Hb Duarte with those of HbA, and
22 through proton NMR and molecular dynamics simulations we have investigated their tertiary and quaternary structures. The variant exhibits an increased oxygen affinity with a normal Hill coefficient and Bohr effect. The abnormal function of Hb Duarte is attributed to the presence of a proline residue at the b62 position, since the functional properties of another Hb variant in the same position, Hb J-Europa (b62Ala/Asp), have been described as normal. Thereafter 1H-NMR studies have shown that the b62 Ala/Pro substitution causes structural modifications of the tertiary structure of the b globins, leaving the quaternary structure unaltered. These results have been confirmed by extensive all-atom molecular dynamics simulations. All these findings lead to the conclusion that the b62 Ala/Pro substitution produces a destabilization of the E-helix extending downward to the CD corner. Particularly, a cavity near the distal histidine of the b-chains, connecting the heme pocket to the solvent, is affected, altering the functional properties of the protein molecule
IDENTIFICATION AND CHARACTERIZATION OF A NEW DOUBLE VARIANT HEMOGLOBIN (HbG-PHILADELPHIA/DUARTE ALFA2 68 ASN→LYS BETA2 62ALA→PRO
No full text
