Detection of Hb H disease caused by a novel mutation and --^SEA deletion using capillary electrophoresis

Hb H disease is a serious type of α-thalassemia which cause moderate anemia while misdiagnosis by routine genetic analysis in a rare or novel Hb H disease.

The study was done on three patients and one fetus in a suspected Hb H disease family. Hb analysis was carried out using capillary electrophoresis (CE), and hematological analysis was conducted with an automated cell counter. Common α- and β-thalassemia mutations were detected by routine genetic analysis (gap-PCR and RDB-PCR). Novel mutation diagnostic methods were based on DNA sequencing.

Capillary electrophoresis revealed clinical feature of classic Hb H disease in the proband, and hematology analysis showed moderate anemia (Hb 87 g/L). But routine genetic analysis was found that it was only a heterozygote for the --^SEA deletion. DNA sequencing of α-globin genes (α1 and α2) identified the breakpoints between nts 34162 and 34171 at α2 gene, named CD 90-93 (-AGCTTCGG) mutation. The genotype of proband and fetus was the same --^SEA /-α^CD90-93 . His father was homozygous for the novel mutation (-α^CD90-93 /-α^CD90-93 ), and his mother was heterozygote for the --^SEA deletion.

Our study for the first time described the novel mutation CD 90-93 (-AGCTTCGG). CE is a way to avoid misdiagnosis of rare or novel Hb H disease.