Identification of the Linkage of a 1.357 KB β-Globin Gene Deletion and A γ-Globin Gene Triplication in a Chinese Family

Abstract

The 1.357 kb β-globin gene deletion was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. Interestingly, this form of the deletion was linked to a –^Gγ–^AGγ–^Aγ triplication. The proband, a compound heterozygote for this linked mutant gene and a β-globin gene [−28 (A>G)] mutation, had a phenotype of β-thalassemia intermedia (β-TI). She was not transfusion dependent and had the following parameters: a Hb level of 5.3 g/dL, 72.8% Hb F and 55.1% ^Gγ chain in Hb F. Four members of the family, who were carriers of this linked mutant gene, had a hematological phenotype of β⁰-thalassemia (β⁰-thal) with high Hb F and low ^Gγ chain values. RNA analyses showed decreased levels of β-globin mRNA and increased levels of γ-globin mRNA in heterozygotes. Haplotype analyses indicated that the unusual form of the β-globin gene deletion and γ-globin gene triplication in cis were linked to halotype [+ – – – – – –].

Keywords:

• β-Thalassemia intermedia (β-TI)
• β-Globin gene deletion
• γ-Globin gene triplication
• ^AGγ Hybrid gene