新的珠蛋白基因突变引起少见地中海贫血四例报告及文献复习

OBJECTIVE: To analyze the DNA sequences and clinical phenotypes of four cases with rare thalassemia to improve its recognition and accurate diagnosis. METHODS: The DNA sequence characteristics of four cases with rare thalassemia diagnosed from May 2014 to December 2019 were retrospectively analyzed, and related literature was reviewed. RESULTS: The results of the routine gene test for thalassemia indicated that the common three type of deletion and three point mutations in hemoglobin alpha 1/2（HBA1/A2）, and 16 point mutations in hemoglobin beta（HBB）gene were unable to be detected in cases 1–3, and case 4 was -- SEA. However, the results of HBA1/A2 and HBB whole-genome sequencing revealed that the four cases had a point mutation of HBB:c.347C>A, HBB:c.1A>G, HBB: c.393T>G, and HBA2: c.301-1G>A（IVS II-142 G>A）, respectively. Meanwhile, the father, aunt, and grandfather of case 2 carried the HBB:c.1 A>G heterozygous point mutation. CONCLUSION: The novel mutations in HBB and HBA2 genes, resulting in a rare thalassemia, were revealed. Among them, the HBB: c.347C>A, HBB:c.1A>G, and HBA2:c.301-1G>A（IVS II-142 G>A）mutations were first reported in Chinese patients with thalassemia. Contrarily, HBB:c.393T>G mutation has not yet been recorded in the databases of human hemoglobin variants and thalassemia. The discovery of these novel nucleotide variants in this study would enrich the DNA mutation gene database of thalassemia.