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Hb Palencia: a novel δβδ-type two-way fusion variant with β-globin-like expression levels
  1. Jorge M Nieto1,
  2. Fernando Ataúlfo González1,
  3. José María Alonso2,
  4. Eva Golvano2,
  5. Lucia Guerrero2,
  6. Beatriz Albarrán2,
  7. Ana villegas1,
  8. Rafael B Martínez1,
  9. Paloma Ropero1
  1. 1 Hematology, Hospital Clínico San Carlos, Madrid, Spain
  2. 2 Hematology, Complejo Asistencial Universitario, Palencia, Spain
  1. Correspondence to Dr Paloma Ropero, Hematology, Hospital Clínico San Carlos, Madrid 28040, Spain; paloma.ropero{at}salud.madrid.org

Abstract

Aims Fusion proteins of unequal recombination events at the β-globin locus have pathological effect. The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by β-like globin chains with a δ-globin (HBD) N-terminus and a β-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 β-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 β-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 βδβ-type variant suggests transcriptional control by HBB elements and a half-life similar to normal HBB.

  • HPLC
  • electrophoresis capillar
  • hemoglobinopathies
  • molecular diagnosis

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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors All the authors have contributed in the writing of the manuscript and in the assembly of the figures.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee of the Hospital Clínico San Carlos (Madrid, Spain).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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