The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30 kb deletion (patient 1) we refer to as - -(JAL) and a large 216 kb deletion (patient 2) we refer to as - -(LOD). Patient 1 was a compound heterozygote for - -(JAL) and -α(3.7) (rightward deletion). Twelve family members of patient 1 carrying the - -(JAL) deletion were available for evaluation: five with - -(JAL)/-α(3.7), four with - -(JAL)/α(Hph I)α and three with - -(JAL)/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (- -(LOD)/-α(3.7)), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.
Keywords: deletion; α-Globin gene cluster; α-thalassemia (α-thal).