探讨广州北部地区αβ复合型地中海贫血人群基因突变类型和血液学特征。

选择2018年1月至2019年12月在广州市花都区妇幼保健院进行地中海贫血基因检测的门诊、住院和体检的广州北部地区14 600例受检者，采用血常规联合血红蛋白电泳分析对受检者进行地中海贫血血液学筛查，对于初筛阳性者采用跨越断裂点聚合酶链式反应(Gap-PCR)＋导流杂交法检测常见α和β-地中海贫血基因型，对于少见型则采用三联体电泳或基因测序法进一步检测，在αβ复合型地中海贫血组(n＝254)患者中选择临床表现为β-地中海贫血的患者(n＝250)，与采用随机数字表法选取的单纯β-地中海贫血组(n＝250)进行血液学指标比较。

在14 600例受检者中检测出254例αβ复合型地中海贫血基因携带者，群体发生率为1.74%(254/14 600)；共检出41种αβ复合型地中海贫血基因型，以--^SEA/αα复合β^IVS-Ⅱ-654/β^N最多(40例)，其次是--^SEA/αα复合β^CD41-42/β^N(32例)，-α^3.7/αα复合β^CD41-42/β^N(25例)居第三位；在254例αβ复合型地中海贫血患者中，有250例患者表现为β-地中海贫血，对其红细胞(RBC)[(5.62±0.74) ×10¹²/L]、平均红细胞体积(MCV)[(67.64±5.52)fl]、平均红细胞血红蛋白含量(MCH)[(21.68±1.73)pg]与单纯β-地中海贫血组[(6.10±0.85)×10¹²/L，(63.61±5.01)fl，( 20.49±1.89)pg]比较，均差异有统计学意义(t＝4.86，－6.14，－5.24;均P<0.01)；而血红蛋白(HGB)[(121.52±14.67)g/L]和血红蛋白A₂(HbA₂)[(5.23±0.51)%]与单纯β-地中海贫血组[(124.42±15.20)g/L，(5.29±0.55)%]比较，均差异无统计学意义(t＝1.55，0.79；均P>0.05)。

广州北部地区αβ复合型地中海贫血基因型复杂多样，发病率高，具有高度的遗传异质性和多样性，缺乏特异性的血液学指标。血液学表型与基因检测结果不相符时，要考虑存在罕见型地中海贫血的可能，αβ复合型地中海贫血基因型的确诊还需依靠分子诊断的方法。

To explore the genotypes and hematological characteristics of patients with αβ-thalassemia in the northern of Guangzhou.

Outpatients, inpatients, and physical examination patients who underwent genetic testing of thalassemia (n=14 600) in the Huadu District Maternal and Child Healthcare Hospital in Guangzhou from January 2018 to December 2019 were enrolled. The patients were screened by blood routine test and hemoglobin electrophoresis analysis, α-thalassemia and β-thalassemia genotypes were detected by Gap-PCR and flow-through hybridization technology among the positive samples by the primany screening, and genetic sequencing methods were used for rare genotypes. Statistical analysis was carried out on the hematological indicators of αβ-thalassemia group whose clinical manifestations were β-thalassemia (n=250) and pure β-thalassemia group (n=250) who were selected randomly.

Two hundred and fifty-four cases of αβ-thalassemia were detected in 14 600 subjects with a population incidence of 1.74% (254/14 600). A total of 41 genotypes were detected, the most prevalent genotype was --^SEA/αα and β^IVS-Ⅱ-654/β^N(40 cases), the next was --^SEA/αα and β^CD41-42/β^N(32 cases), and -α^3.7/αα and β^CD41-42/β^N(25 cases) ranked third. Among 254 cases of αβ-thalassemia group, there were 250 cases with clinical manifestations of β-thalassemia. Red blood cells (RBC) [(5.62±0.74)×10¹²/L], mean corpuscular volume (MCV)[(67.64±5.52)fl], mean corpuscular hemoglobin (MCH) [(21.68±1.73)pg] in αβ-thalassemia group (n=250) were compared with those in pure β-thalassemia group (n=250) [(6.10±0.85)×10¹²/L, (63.61±5.01) fl, (20.49±1.89)pg], the differences were statistically significant (t=4.86, -6.14, -5.24, all P<0.01). Hemoglobin (HGB) [(121.52±14.67)g/L] and hemoglobin A₂ (HbA₂) [(5.23±0.51)%] in αβ-thalassemia were compared with pure β-thalassemia group [(124.42±15.20)g/L, (5.29±0.55)%], there were no significant differences (t=1.55, 0.79, all P>0.05).

The αβ-thalassemia genotype in northern of Guangzhou is complex and diverse, with high incidence rate, high genetic heterogeneity and diversity, and lacks specific hematological indicators for diagnosis. When hematological phenotype and genotype are inconsistent, rare genotypes should be considered, αβ-thalassemia genotype diagnosis must be rely on molecular diagnosis methods.