Abstract
In the present study, a rare familial case of severe thalassemia with compound spontaneous mutations is reported. A 2.5‑year‑old boy, who suffered from severe anemia with yellowish skin, enlarged liver and spleen, was provided with a blood transfusion every 20 days to maintain hemoglobin levels between 90 and 100 g/l. Sanger sequencing combined with reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and Gap‑PCR revealed that the proband was a carrier of 4 compound heterozygous mutations: Hemoglobin subunit β (HBB):IVS‑II‑654(C>T)β+; Southeast Asian‑type‑hereditary persistence of fetal hemoglobin (SEA‑HPFH); HBB:c316‑148G>T; hemoglobin subunit α2 (HBA2):c.46G>A. The father of the proband was identified as a carrier of the heterozygous SEA‑HPFH mutation, the mother was a carrier of compound heterozygous mutations of HBB:IVS‑II‑654(C>T) and HBA2:c.46G>A, and the elder sister was heterozygous for HBB:IVS‑II‑654(C>T)β+. Based on these genetic results, it was determined that the proband had both of heavy β‑thalassemia and α‑thalassemia. Upon human leukocyte antigen matching, bone marrow transplantation (BMT) was successfully performed on the proband by selecting his HLA‑compatible sister as a donor. Following treatment, the proband was revealed to only carry the IVS‑II‑654(C>T)β+ heterozygous mutation, and further regular blood transfusions have been avoided; BMT results remained normal at six months follow‑up.