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

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 -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 9.7kb 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 (0)-thalassemia ((0)-thal) mutation. There would be a 25.0% chance of conceiving an -thal intermedia or -thal major (-TI or -TM) fetus if the couples are both carriers. Rare large deletions can cause -thalassemia (-thal) and the structure analysis of an unknown deletion is important for clinical diagnosis and further genetic counseling.