The IVS-II-1 (G → A) β0-Thalassemia Mutation in CIS with Hb A2-Troodos [δ116(G18)Arg → Cys (CGC → TGC)] Causes a Complex Prenatal Diagnosis in an Iranian Family

Abstract

The β-thalassemia (thal) minor phenotypes with normal Hb A2 levels and decreased MCV and MCH values are relatively rare β-thal traits. Here, we describe a family with normal Hb A2 and decreased MCV and MCH levels. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) revealed the IVS-II-1 (G→A) mutation in the β-globin gene of the proband and her father. Direct sequencing of the δ-globin gene of the proband and her father also revealed a previously reported variant called Hb A2-Troodos [δ116(G18)Arg→Cys] [in cis with the IVS-II-1 (G→A) β0-thal mutation]. This is the first case report of Hb A2-Troodos in association with the β0 IVS-II-1 mutation. Reduced Hb A2 expression by a concomitant Hb A2 β-thal in cis or trans, may cause problems in carrier diagnostics, and eventually in genetic counseling and prenatal diagnosis when insufficient molecular analyses are performed.