A rare thalassemia intermedia case caused by co-existence of Hb H disease (--~(SEA)/-α~(4.2)) and β-thalassemia major (β~(CD17A)>T/β~(IVS2-654C)>T):implications for prenatal diagnosis

Objective To analyze the relation between the genotype and phenotype in a Chinese patient with thalassemia intermedia and its implications for prenatal diagnosis and genetic counseling of thalassemia intermedia caused by co-existence of Hb H disease and β thalassemia major. Methods Phenotypic analysis was performed using standard hematological tests to measure red blood cell parameters and Hb concentration. Genotyping of β thalassemia mutations and α thalassemia deletion were conducted using reverse dot-blot (RDB) assay and gap-PCR,respectively. We investigated the pathogenesis of this case by genotype-phenotype correlation analysis based on screening of the patient's family members. Prenatal diagnosis for a high-risk fetus in this family was performed by amniotic fluid DNA analysis. Results The proband was identified as a patient with severe thalassemia intermedia caused by co-existence of Hb H disease (--SEA/-α4.2) and β-thalassemia major (βCD17AT/βIVS2-654CT),whose father was heterozygous for β thalassemia (βCD17AT/βN) and α-thalassemia trait (--SEA/) and the heterozygous for β thalassemia (βIVS2-654CT /βN) and silent α-thalassemia (-α4.2/). The result of prenatal diagnosis showed co-existence of β thalassemia major and silent α thalassemia in the high-risk fetus,and the parents requested termination of pregnancy after genetic counseling. Conclusions We report for the first time a rare thalassemia intermedia case resulting from 4 complex α/β thalassemia combination and the molecular pathogenesis of thalassemia intermedia is updated in the Chinese population. The practice of prenatal diagnosis in this case may also provide reference for diagnosis of similar cases.