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 [+ – – – – – –].