The Rare Hb Showa-Yakushiji [β110(G12)Leu→Pro, CTG→CCG] in Combination with an α Gene Triplication Found in a Dutch Patient During Her First Pregnancy Examination

Abstract

We report a semi dominant β-thalassemia (thal) phenotype caused by the rare Hb Showa-Yakushiji [β110(G12)Leu→Pro, CTG→CCG] mutation in combination with an α gene triplication. This combination of two rare mutations was observed during hemoglobinopathy carrier diagnostics in a 26-year-old Dutch female at 9 weeks gestation, at the first pregnancy examination in the midwives practice. The partner was promptly examined and no abnormalities were found. The β-thal trait was diagnosed by a standard high performance liquid chromatography (HPLC) procedure showing a normal separation but an elevated Hb A2 level of 5.9% in the presence of pronounced hypochromic microcytic parameters and mild chronic hemolysis. Direct sequencing of the β-globin genes was subsequently performed revealing a CTG→CCG transition at codon 110. This rare mutation was previously described as two independent events in a few Japanese and Indian individuals. The mutation induces a Leu→Pro substitution and the gene product is highly unstable. Gap-polymerase chain reaction (gap-PCR) revealed a heterozygosity for the α gene triplication as well. The excess of α-globin chains contributed only marginally to the hematological abnormalities of the patient and did not aggravate the phenotype to an intermediate level.