Prenatal diagnosis of a rare β ‐thalassemia gene －90 (C>T) ( HBB : c.‐140 C>T) mutation associated with deletional Hb H disease (‐‐ SEA /‐ α 4.2 )

Abstract 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 α 0 ‐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 α 0 ‐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 [‐ α 4.2 (leftward)] from the father. Conclusion We reported a rare 90 (C>T) ( HBB : c.‐140 C>T) mutation combined with the ‐‐ SEA /‐ α 4.2 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.