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Haemoglobinopathies that occur with decreased HbA2 levels: a gene mutation set involving the δ gene at a Spanish centre
  1. Ana Villegas1,
  2. Fernando Ataúlfo González1,
  3. Jorge M Nieto1,
  4. Félix de la Fuente-Gonzalo1,
  5. Rafael Martínez1,
  6. María Josefa Torrejón2,
  7. Paloma Ropero1
  1. 1Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, IdISS, Madrid, Spain
  2. 2Servicio de Análisis Clínicos, Hospital Clínico San Carlos, Madrid, Spain
  1. Correspondence to Dr Paloma Ropero, Hospital Clínico San Carlos, Servicio de Hematología, Sección Eritropatología, C/ Profesor Martín Lagos s/n, Madrid 28040, Spain; paloma.ropero{at}salud.madrid.org

Abstract

Aims Haemoglobin A2 (HbA2) consists of two globin chains, α and β. Alterations in any of these genes influences the level of HbA2. Here, we present cases of structural Hb variants and thalassaemias which present either alone or together and reduce the level of HbA2 at varying degrees. Furthermore, we present a novel structural mutation in the δ globin gene, called Hb A2-Madrid.

Methods The levels of HbA2 and HbF and the different haemoglobin variants were measured and analysed by ion exchange high performance liquid chromatography (HPLC, VARIANT II), the types of haemoglobins were determined by capillary zone electrophoresis (CZE) (Sebia) and the globin chains were determined by reversed-phase HPLC. Genetic analysis was performed by automatic sequencing of the α and δ genes as well as by multiple PCRs for the α globin genes.

Results In α thalassaemia (n=94), the HbA2 levels ranged from 1.39% to 2.43%. Among individuals with δ thalassaemia (n=5), the HbA2 level of those with δ+ thalassaemia was 1.77%, and that of those with δ0 thalassaemia was 1.70%. Among the individuals with δβ thalassaemia (n=13), those who were homozygous lacked HbA2. All structural haemoglobinopathies (n=97) were heterozygous; the α chain variants (n=84) presented with an HbA2 level of 1.76%, while the δ chain variants (n=13) presented with a level of 1.75%.

Conclusion HbA2 is an essential parameter in the diagnostics of haemoglobinopathies. HPLC-EC and CZE allow the quantification of HbA2. Here, we show that quantification of HbA2 is critical for the identification of α, δ and βδ thalassaemias. Structural variants are discovered by HPLC. Molecular genetics is required for the proper identification of the mutations. Only with this knowledge is genetic counselling possible.

  • DNA
  • HAEMOGLOBINOPATHY
  • THALASSAEMIA

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Footnotes

  • Handling editor Mary Frances McMullin

  • Funding This study has been supported in part by grants from Instituto de Salud Carlos III (PI12/01068).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics committee of Hospital Clínico San Carlos (CP-CI 15/462-E).

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

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