Hb Palencia: a novel δßδ-type two-way fusion variant with ß-globin-like expression levels.
J Clin Pathol
; 72(1): 46-51, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30315135
ABSTRACT
AIMS:
Fusion proteins of unequal recombination events at the ß-globin locus have pathological effect. The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by ß-like globin chains with a δ-globin (HBD) N-terminus and a ß-globin (HBB) C-terminus, whereas reciprocal products of underlying crossover events hold a HBB N-terminus and HBD C-terminus instead. Finally, Hb Parchman contains a ß-like globin chain with a central HBB fragment and HBD-derived N-termini and C-termini, whereas reciprocal hybrid proteins are as yet unknown.METHODS:
The propositus was an 80-year-old Caucasian man, whose HbA1c quantification by HPLC (Variant II turbo) for exclusion of type-2 diabetes revealed an abnormal peak. Haemoglobins were analysed by ion-exchange HPLC (Variant II) and capillary electrophoresis (Sebia Capillarys Flex) and DNA by automatic Sanger sequencing of δ-globin and ß-globin genes.RESULTS:
Sequencing showed an HBB-HBD-HBB hybrid gene, with HBD-derived central codons 9-31, and HBB-derived UTRs and complementary coding regions. The corresponding new hybrid haemoglobin (Hb Palencia) is represented at ≈40%, similar to HbA.CONCLUSION:
Hb Palencia contains the first globin variant with internal HBD sequences and HBB-derived N-terminal and C-terminal and regulatory sequences. Relative quantity of the new ßδß-type variant suggests transcriptional control by HBB elements and a half-life similar to normal HBB.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Hemoglobinas Anormais
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Globinas beta
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Globinas delta
Limite:
Aged80
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article