Delta 0-talasemia por inserción de 27 pares de bases en el gen o-globina con descenso de los valores de hemoglobina A2 / Delta 0-thalassemia by insertion of 27 base pairs in o-globin gene with decreased hemoglobin A2 levels

Fundamento y objetivo: Se describe una nueva mutación en el gen δ-globina (delta-talasemia), responsable de una disminución de los valores de hemoglobina (Hb) A2 y asociada a Hb Watts, variante de Hb debido a una deleción de trinucleótidos. Pacientes y método: El análisis de Hb se llevó a cabo mediante high performance liquid chromatography (HPLC, «cromatografía líquida de alta resolución») de intercambio iónico y electroforesis capilar de zona. Se utilizaron técnicas de reacción en cadena de la polimerasa y secuenciación automática para identificar las mutaciones en los genes δ- y α-globina. Resultados: La Hb anómala se observó en la electroforesis capilar de zona en Z6 y por HPLC de intercambio iónico apareció un pico más lento que la HbA en un tiempo de retención de 4,19 min. Esta variante de la Hb se llama Hb Watts [α2 74(EF3)Asp->0 o α2 75(EF4)Asp->0; HBA2:c.226_228delGAC]. El bajo porcentaje de HbA2 se debe a una inserción de 27 nt entre los nucleótidos 83 y 84 de IVS-I del gen de δ-globina. Conclusiones: Cuando se analiza un cromatograma se debe tener en cuenta la posibilidad de una delta-talasemia o una variante de HbA2, aparte de una alfa-talasemia, beta-talasemia y hemoglobinopatías estructurales. A tal fin, cada uno de los picos y sus porcentajes deben ser considerados para una correcta interpretación y evitar diagnósticos erróneos tanto como sea posible (AU)

Background and objective: We describe a novel delta-thalassemia mutation causing decreased hemoglobin (Hb) A2 levels associated with Hb Watts, variant Hb resulting from a trinucleotide deletion in Spain. Patients and method: Hb variant analysis was performed by cation-exchange high performance liquid chromatography (HPLC) and capillary zone electrophoresis. Polymerase chain reaction and DNA sequence analyses were used to identify mutations in the δ- and α-globin genes. Results: Abnormal Hb was observed on capillary zone electrophoresis in Z6 and by cation-exchange HPLC a slower peak than HbA was observed at an retention time of 4.19 min. This variant Hb is called Hb Watts [α2 74(EF3)Asp->0 or α2 75(EF4)Asp->0; HBA2:c.226_228delGAC]. The decreased HbA2 percentage owes to an insertion of 27 nt between nt 83 and 84 of IVS-I of the δ-globin gene. Conclusions: When analyzing a chromatogram, the possibility of the existence of delta-thalassemia or an HbA2 variant should be considered, apart from alfa-, beta-thalassemia and structural haemoglobinopathies. To this end, each of the peaks and their percentages should be considered to allow for correct interpretation and to avoid misdiagnosis as much as possible (AU)

[Delta°-thalassemia by insertion of 27 base pairs in δ-globin gene with decreased hemoglobin A2 levels]. / Delta(0)-talasemia por inserción de 27 pares de bases en el gen δ-globina con descenso de los valores de hemoglobina A2.

BACKGROUND AND OBJECTIVE: We describe a novel delta-thalassemia mutation causing decreased hemoglobin (Hb) A2 levels associated with Hb Watts, variant Hb resulting from a trinucleotide deletion in Spain. PATIENTS AND METHOD: Hb variant analysis was performed by cation-exchange high performance liquid chromatography (HPLC) and capillary zone electrophoresis. Polymerase chain reaction and DNA sequence analyses were used to identify mutations in the δ- and α-globin genes. RESULTS: Abnormal Hb was observed on capillary zone electrophoresis in Z6 and by cation-exchange HPLC a slower peak than HbA was observed at an retention time of 4.19min. This variant Hb is called Hb Watts [α2 74(EF3)Asp->0 or α2 75(EF4)Asp->0; HBA2:c.226_228delGAC]. The decreased HbA2 percentage owes to an insertion of 27nt between nt 83 and 84 of IVS-I of the δ-globin gene. CONCLUSIONS: When analyzing a chromatogram, the possibility of the existence of delta-thalassemia or an HbA2 variant should be considered, apart from alfa-, beta-thalassemia and structural haemoglobinopathies. To this end, each of the peaks and their percentages should be considered to allow for correct interpretation and to avoid misdiagnosis as much as possible.