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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. 1Hematology, Hospital Clínico San Carlos, Madrid, Spain
  2. 2Hematology, Complejo Asistencial Universitario, Palencia, Spain
  1. Correspondence to Dr Paloma Ropero, Hematology, Hospital Clínico San Carlos, Madrid 28040, Spain; paloma.ropero{at}


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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  • 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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