Abstract:

Objective To analyze the molecular characteristics and phenotypes of rare variation of thalassemia gene. Methods A total of 8 329 patients were identified for α- and β-globin gene by gap-polymerase chain reaction（Gap-PCR）,polymerase chain reaction-reverse dot blot（PCR-RDB） and DNA sequencing. The patients with rare variation were processed with the analysis of red blood cell（RBC） parameters and hemoglobin（Hb） electrophoresis. Results A total of 13 kinds of rare variation were identified. Rare deletion in α-globin included HKαα/αα or HKαα/-α^3.7,HKαα/--SEA and --THAI/αα. Rare mutation in α-globin included CD15 and CD118. Rare deletion in β-globin included ^Gγ⁺（^Aγδβ）⁰,SEA-HPFH and Taiwanese. Rare mutation in β-globin included CD37,IVS-Ⅰ-2,IVS-Ⅰ-114,IVS-Ⅱ-81 and -90. Mean corpuscular volume（MCV） and mean corpuscular hemoglobin（MCH） of HKαα/--SEA and THAI/αα samples were reduced,and the HbA₂ levels were in normal range. The MCV and MCH of ^Gγ⁺（^Aγδβ）⁰,SEA-HPFH,Taiwanese,^Gγ⁺（^Aγδβ）⁰ composited -α^3.7 heterozygote and SEA-HPFH composited --SEA heterozygote samples were reduced,the HbF levels were increased,the HbA₂ level of ^Gγ⁺（^Aγδβ）⁰ was normal,and the HbA₂ levels of the other types were increased. The MCV and MCH of CD37,IVS-Ⅰ-2,IVS-Ⅰ-114,HKαα/αα or HKαα/-α^3.7 composited -28 heterozygote and -90 composited --SEA heterozygote samples were reduced,and the HbA₂ levels were increased. The heterozygote of other rare types had normal hematological phenotype. Conclusions HKαα/αα or HKαα/-α^3.7presents with silent α-thalassemia phenotype,and HKαα/--SEA and -THAI/αα presents with light α-thalassemia phenotype in the variation of α-gene. ^Gγ⁺（^Aγδβ）⁰,SEA-HPFH,Taiwanese,^Gγ⁺（^Aγδβ）⁰ composited -α^3.7heterozygote,SEA-HPFH composited --SEA heterozygote,CD37,IVS-Ⅰ-2,IVS-Ⅰ-114 and -90 composited --SEA heterozygote in the variation of β-gene presents with light β-thalassemia phenotype.

Key words: Thalassemia, Globin, Variation, Phenotype