A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS

In this report we decribed a new alpha-chain variant found during the measurement of hemoglobin A(1c) (Hb A(1c)) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an alpha-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A(1c) measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.

Automated summary

In this report, a new alpha-chain variant of hemoglobin A(1c) was discovered through matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry analysis. This variant, with a mass of 15,155 Da, was not detected using cation-exchange high-performance liquid chromatography and capillary electrophoresis methods. Sanger sequencing confirmed the presence of a heterozygous missense mutation, which resulted in a mass difference of 28 Da due to the substitution of alanine with valine. The mutation was named Hb Tangshan after the proband's residence.