Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia.

Autor: Ropero P; Hematology Service, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain. paloma.ropero@salud.madrid.org.; Instituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, Spain. paloma.ropero@salud.madrid.org., González Fernández FA; Hematology Service, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain., Nieto JM; Hematology Service, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain.; Instituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, Spain., Recasens V; Hematology Service, Hospital Universitario Miguel Servet, Zaragoza, Spain., Montañés Á; Hematology Service, Hospital Universitario Miguel Servet, Zaragoza, Spain., Murúzabal MJ; Hematology Service, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain., Sarasa M; Hematology Service, Hospital Comarcal de Laredo, Laredo, Cantabria, Spain., Fernández C; Hematology Service, Hospital Comarcal de Laredo, Laredo, Cantabria, Spain., Villegas A; Hematology Service, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain., Benavente CC; Hematology Service, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, 28040, Madrid, Spain.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2022 Jul; Vol. 101 (7), pp. 1465-1471. Date of Electronic Publication: 2022 Apr 25.
DOI: 10.1007/s00277-022-04837-4
Abstrakt: Most β-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 β-globin gene that cause β 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 β-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-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] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [β 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 β 0 -thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the β-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.)
Databáze: MEDLINE
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