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Hemoglobin. 2019 Mar;43(2):77-82. doi: 10.1080/03630269.2019.1601107. Epub 2019 Jun 13.

A Homozygous Mutation on the HBA1 Gene Coding for Hb Charlieu (HBA1: c.320T>C) Together with β-Thalassemia Trait Results in Severe Hemolytic Anemia.

Author information

1
a Department of Blood Cell Research , Sanquin Research and Landsteiner Laboratory, University of Amsterdam , Amsterdam , the Netherlands.
2
b Laboratory for Red Blood Cell Diagostics , Sanquin , Amsterdam , The Netherlands.
3
c Department of Hematology , PeyvandLab Complex , Shiraz , Iran.
4
d Hematology Research Center, Shiraz University of Medical Sciences , Shiraz , Iran.
5
e Department of Hematopoiesis , Sanquin Research and Landsteiner Laboratory, University of Amsterdam , The Netherlands.
6
f Department of Molecular and Cellular Hemostasis , Sanquin Research and Landsteiner Laboratory, University of Amsterdam , Amsterdam , The Netherlands.
7
g Department of Biomolecular Mass Spectrometry and Proteomics , Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University , Utrecht 3584 CS , The Netherlands.

Abstract

A 4-year-old boy, a β-thalassemia (β-thal) carrier, with an unexplained severe chronic microcytic anemia was referred to us. Sequencing of the α-globin genes revealed a Hb Charlieu [α106(G13)Leu→Pro, HBA1: c.320T>C, p.Leu107Pro] mutation present on both HBA1 genes. Quantitative polymerase chain reaction (qPCR) confirmed αCharlieu mRNA in the proband and his parents, showing that the mutation does not affect mRNA stability. However, we were unable to detect the Hb Charlieu protein by capillary electrophoresis (CE), reverse phase electrophoresis, cation exchange electrophoresis or isoelectric focusing. Mass spectrometry (MS) allowed us to confirm the presence of the Hb Charlieu peptide in erythrocyte progenitors. These findings suggest that the mutation affects the stability of αCharlieu. As hemoglobin (Hb) heat stability tests showed no abnormalities in erythrocytes, we speculated that αCharlieu is already degraded during red blood cell (RBC) development. The clinical severity in the proband and the presence of new methylene blue-stained aggregates in his reticulocytes indicates that incorporation of αCharlieu destabilizes Hb. This, combined with an excess of unstable free α-globins as the result of β-thal minor, results in severely impaired erythropoiesis and, as a consequence, severe and chronic microcytic anemia in the proband.

KEYWORDS:

Hb Charlieu; anemia; erythrocyte; hemoglobin (Hb); α-Thalassemia (α-thal); β-thalassemia (β-thal)

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