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Strong Positive Dichlorophenolindophenol Precipitation Suggests Hb Dhonburi (or Hb Neapolis) (HBB: c.380T>G) Inheritance in a Couple at Risk for Severe β-Thalassemia

Abstract Hb Dhonburi (also known as Hb Neapolis) (HBB: c.380T>G) is an unstable hemoglobin (Hb) variant that cannot be detected by high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) in routine laboratory diagnosis. This could lead to prenatal misdiagnosis unless a molecular analysis is applied. Here, we report a Thai couple with a positive result for the dichlorophenolindophenol precipitation (DCIP) screening test. After routine laboratory investigation, the female was diagnosed with heterozygous Hb E (HBB: c.79G>A) during pregnancy; however, the male, whose case we present herein, was suspected to carry a rare heterozygous β-thalassemia (β-thal). Therefore, they were designated as a couple at-risk for having a fetus with a serious thalassemia genotype: compound heterozygosity for Hb E with β-thal (Hb E/β-thal). Based on the result of the DCIP test, his DNA was sequenced for a causative mutation and revealed heterozygosity for a rare Hb variant, Hb Dhonburi. Theoretically, this couple was not at risk for Hb E/β-thal. Furthermore, this case demonstrates for the first time that in addition to a common Hb variant, i.e. Hb E, Hb Dhonburi (Hb Neapolis) also gives positive DCIP results, even in the heterozygous state.