Identification of a Novel 9.7 kb Deletion Causing α0-Thalassemia in Two Pregnant Women in Southern China

Abstract

The technique of combining multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (CGH) and gap-polymerase chain reaction (gap-PCR) is an effective way to locate unknown breakpoints on the α-globin genes. In the current report, a novel deletion was detected in two pregnant women with moderate hematological phenotypes. Multiplex ligation-dependent probe amplification and array CGH revealed a probable 9.7 kb deletion at 16p13.3. The breakpoints were precisely defined by gap-PCR and direct sequencing. This deletion (NG_000006.1: g.32709_42418del) included HBA1, HBA2 and HBQ, which resulted in an α0-thalassemia (α0-thal) mutation. There would be a 25.0% chance of conceiving an α-thal intermedia or α-thal major (α-TI or α-TM) fetus if the couples are both carriers. Rare large deletions can cause α-thalassemia (α-thal) and the structure analysis of an unknown deletion is important for clinical diagnosis and further genetic counseling.