Hb Dhonburi (Neapolis) [β126(H4)Val→Gly] Identified in a Family from Northern Iran

Thalassemias are the most common hereditary diseases in Iran, resulting from synthesis defects in one or more hemoglobin (Hb) subunits. The majority of patients suffer from β-thalassemia (thal), but cases with microcytic hypochromic anemia and normal electrophoretic patterns are suspected to have α- or silent β-thal. A family from the northern part of Iran, an area highly prevalent for thalassemias, was referred to us for prenatal diagnosis. The hematological data of the father indicated a pattern of β-thal minor. Reverse hybridization analysis for the most common β-globin mutations identified IVS-II-1 (G→A) in the heterozygous state. The maternal laboratory data indicated a case more compatible with α-thal. Iron deficient anemia was ruled out, and common α-thal point mutations and deletions were investigated. As no mutation was detected, chain synthesis was performed and showed an α β chain ratio of 2.1, that was in the range of β-thal minor. DNA sequencing of the entire β-globin gene identified a heterozygous GTG→GGG (Val→Gly) mutation at codon 126, also known as Hb Dhonburi (Neapolis). Prenatal diagnosis of the fetal DNA showed the absence of the IVS-II-1 and codon 126 anomalies. This result demonstrates the importance of screening of individuals with mild microcytic hypochromic anemia for both α- and silent β-thal mutations.