Detection of Hb H disease caused by a novel mutation and ‐‐(SEA) deletion using capillary electrophoresis

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.