First Report of a Dominantly Inherited β-Thalassemia Caused by a Novel Elongated β-Globin Chain

Abstract

A distinct set of mutations on the β-globin gene leads to dominantly inherited β-thalassemia (β-thal) that is associated with a disease phenotype in a single mutant copy. We described molecular and hematological characteristics of a novel elongated β-globin chain in combination with a known hemoglobin (Hb) variant (N-Baltimore or HBB: c.286A>G) in cis. The highly unstable Hb variant caused typical features of β-thal major (β-TM) or β-thal intermedia (β-TI) in two members of a family depending on their α-globin genotypes. The β mutant allele of the mother was transmitted in an autosomal dominant fashion to her daughter. They resemble severe forms of β-thal due to ineffective erythropoiesis. Taken together with previously published data, this result indicates that a dominant form of β-thal should be regarded as a phenotypic term of hemoglobinopathies caused by β chain variants that are highly unstable.