IDENTIFICATION OF THE LINKAGE OF A 1.357 KB β-GLOBIN GENE DELETION AND A γ-GLOBIN GENE TRIPLICATION IN A CHINESE FAMILY

The 1.357 kb beta-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-(G)gamma-(AG)gamma-(A)gamma triplication. The proband, a compound heterozygote for this linked mutant gene and a beta-globin gene [-28 (A>G)] mutation, had a phenotype of beta-thalassemia intermedia (beta-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% (G)gamma chain in Hb F. Four members of the family, who were carriers of this linked mutant gene, had a hematological phenotype of beta(0)-thalassemia (beta(0)-thal) with high Hb F and low (G)gamma chain values. RNA analyses showed decreased levels of beta-globin mRNA and increased levels of gamma-globin mRNA in heterozygotes. Haplotype analyses indicated that the unusual form of the beta-globin gene deletion and gamma-globin gene triplication in cis were linked to halotype [+------].