Does size matter? Two new deletions in the HBB gene cause ß<SUP>0</SUP>-thalassemia

Autores de IDIVAL

• María Josefa Muruzabal Sitges

  Autor

  mariajose.muruzabal@scsalud.es

Autores ajenos al IDIVAL

• Ropero P
• González Fernández FA
• Nieto JM
• Recasens V
• Montañés Á
• Sarasa M
• Fernández C
• Villegas A
• Benavente CC

Abstract

Most beta-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the beta-globin gene that cause beta(0)-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II beta-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common alpha-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [ABB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [beta nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with beta(0)-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the beta-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

• Anemia; Genetics; Hemoglobinopathy; Molecular diagnosis; Thalassemia