1.Novel point mutation of the α2-globin gene (HBA2) and a rare 2.4 kb deletion of the α1-globin gene (HBA1), identified in two chinese patients with Hb H disease.
So CC1, Chan AY, Ma ES. Hemoglobin. 2014;38(3):213-5. doi: 10.3109/03630269.2014.894478.
Two Chinese patients with mild and moderate Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2) in addition to the - -(SEA) deletion. One patient was a 41-year old man with mild anemia (Hb 11.3 g/dL). Multiplex ligation-dependent probe amplification (MLPA) revealed a rare 2392 bp deletion involving the entire HBA1 gene. Mapping by gap-polymerase chain reaction (gap-PCR) defined the exact breakpoints of this deletion (HBA1: g36859_39252del2392) and confirmed its identity with a recently reported HBA1 deletion found in a Southern Chinese. The other patient was a 53-year old man with moderate anemia (Hb 9.5 g/dL). Automated direct nucleotide (nt) sequencing identified a novel single nt deletion at codon 40 (HBA2: c.123delG). This leads to a frameshift that modifies the C-terminal sequence to (40)Lys-Pro-Thr-Ser-Arg-Thr-Ser-Thr(47)COOH and the introduction of a stop codon TGA 23 nts downstream. These two cases demonstrate the power of MLPA and direct nt sequencing to detect and characterize rare and novel mutations.
