Prenatal diagnosis of a rare β-thalassemia gene －90 (C>T) (HBB: c.-140 C>T) mutation associated with deletional Hb H disease (--SEA /-α4.2 ).

Background: Hemoglobin H (Hb H) disease can be caused by compound heterozygosity for two different mutations or from homozygotes for mutations, and conventional genetic methods may lead to misdiagnosis when Hb H disease is combined with a rare β-thalassemia.

Methods: Hematology parameters and hemoglobin electrophoresis analysis, gap-polymerase chain reaction (gap-PCR) and reverse dot-blot hybridization (RDB-PCR) were employed to identify common α-thalassemia and Hb H disease. Rare β-thalassemia mutations were detected by DNA sequencing.

Results: Hematological analysis and hemoglobin electrophoresis revealed a mild anemia α0 -thalassemia trait (Hb 90 g/L, MCV 71 fL, and MCH 22.7 pg) compound with β+ -thalassemia trait (MCV 71 fL, MCH 22.7 pg, and HbA2 5.51%) for the pregnant woman. DNA sequencing for the β-globin gene revealed rare a －90 (C>T) (HBB: c.-140 C>T) mutation for the woman. DNA analysis identified that the fetus inherited the α0 -thalassemia mutation [--SEA (Southeast Asian)] and a rare β+ -thalassemia mutation －90 (C>T) (HBB: c.-140 C>T) from the mother, and the α+ -thalassemia mutation [-α4.2 (leftward)] from the father.

Conclusion: We reported a rare －90 (C>T) (HBB: c.-140 C>T) mutation combined with the --SEA /-α4.2 in a family. This finding enriched the mutation spectrum of thalassemia molecular characteristics in China and emphasized the significance in DNA sequencing in mutation screening for the families with thalassemia.