Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China

Abstract

Objectivesβ-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations.DesignA retrospective study.MethodsIn this study, the levels of haemoglobin alpha 2 (HbA2) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects.ResultsHbA levels were significantly higher in men than in women, but there was no significant difference on HbA2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA2≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA2. The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and −28 (A>G) (HBB (β-globin):c.−78A>C) had significantly higher HbA2 values compared with other β-thalassaemia.ConclusionsEthnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China.

Molecular epidemiology, pathogenicity, and structural analysis of haemoglobin variants in the Yunnan province population of Southwestern China

“…There are 15 variants were found to be “deleterious” by SIFT analysis and seven variants were predicted to be “damaging” by the PolyPhen-2 software prediction model. Some Hb variants such as Hb E, Hb J-Bangkok, and Hb New York had no apparent clinical effects reported by previous report 22,26,28 . And individual of δ-globin gene defects usually has no clinically meaningful problems for low concentration of Hb A 2 regardless of the results of prediction 9,11 .…”

“…So far, the Hb E, HB New York, Hb J-Bangkok, and Hb Queens variants have been the most popular mutations in the Yunnan population. The Hb E, Hb Queens, Hb Q-Thailand, Hb Thailand, Hb J-Bangkok, and Hb J-Lome variants have been mainly prevalent in the Southeastern Asia and Southern China regions 22–27 . The Hb New York variant can be found in Chinese and American subjects 28 , while the Hb J-Kaohsiung variant has been mostly encountered in Thailand and Chinese populatons 29 .…”

Comparison between capillary zone electrophoresis and capillary isoelectric focusing for thalassemia screening in southern China

“…This is not a big problem in the β‐thalassemia diagnosis for adults. Because Hb A2 (whether normal or abnormal) will not exceed 8%, it is not difficult to indentify Hb E when there is a peak located in the area of Hb A2 with the percentage higher than 8%. But as shown in Table , while the specimen was from a fetus or a newborn or a young baby and analyzed by Helena V8, percentage of the peak located in the area of Hb A2 might higher than reference but might not exceed 8%, even not exceed 7%.…”

“…southern China is an area suffers from thalassemia heavily where very high thalassemia gene frequencies can be identified in many provinces, for example 0.01%‐3.17% (α‐thalassemia) and 1.60%‐3.56% (β‐thalassemia) of the population in Sichuan, 3.18%‐9.46% (α‐thalassemia) and 1.60%‐3.56% (β‐thalassemia) in Guangdong and 9.47%‐14.13% (α‐thalassemia) and 3.57%‐6.78% (β‐thalassemia) in Guangxi, etc. In these territories, instead of Hb S which is the most common variant in Europeans and Americans, Hb E and Hb Constant Spring (Hb CS) become the top 2 variants related to β gene abnormity, together with Hb H and/or Hb Barts which are related to α gene abnormity, and form the most essential group of variants which should be identified carefully during hemoglobinopathy screening in southern China . This situation requires methods or instruments used in southern China having the ability to identify trace peaks and distinguish abnormal peaks from normal peaks.…”

“…In these territories, instead of Hb S which is the most common variant in Europeans and Americans, Hb E and Hb Constant Spring (Hb CS) become the top 2 variants related to β gene abnormity, together with Hb H and/or Hb Barts which are related to α gene abnormity, and form the most essential group of variants which should be identified carefully during hemoglobinopathy screening in southern China. [6][7][8][9] This situation requires methods or instruments used in southern China having the ability to identify trace peaks and distinguish abnormal peaks from normal peaks. So in this study, the performance of CIEF equipment Helena V8 platform E-class and CZE equipment Sebia Minicap on identifying Hb E, Hb CS, Hb H and Hb Barts for patients from southern China was compared.…”