Zhong L Y, Wang F, Chen P S, Xie Y J, Tan J Y, Liu M, Huang B, Lin W B
Department of Clinical Laboratoty, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Zhonghua Yi Xue Za Zhi. 2018 Jan 9;98(2):117-121. doi: 10.3760/cma.j.issn.0376-2491.2018.02.009.
To analyze the genotype-phenotype correlations among those thalassemia samples with the presence of -α(3.7,) --(SEA) and normal α(2) alleles on their α-globin gene clusters. Fourteen patients(including 1fetus, 4 males and 9 females, aged 0- 56 years old)who were suspected diagnosed by hematologic analysis and genetic testing among 16 080 participants in our laboratory since from August 2011 to August 2016, were enrolled. Complete blood cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common deletional thalassemia deletions. Reverse dot-blot (RDB) assay was applied for detecting 17 common β-globin gene mutations and three common non-deletional α(2) gene mutations. Two-round nested PCR assay was established to detect the genotype of HKαα in α-thalassemia. Fourteen cases were identified as HKαα/--(SEA) (14/16 080), including a pedigree and a rare case of HKαα/--(SEA) co-inheritance with IVS-Ⅱ-654(C→T) heterozygote. In HKαα/--(SEA) thalassemia group, mean cell volume(MCV) was (69.54±5.92)fl, and mean cell hemoglobin(MCH) was(22.11±2.22)pg and hemoglobin(Hb) was (117.64±18.14) g/L. Compared with normal group, MCV, MCH and Hb in HKαα/--(SEA) thalassemia group, was significantly decreased(<0.05). There were no significant differences between α-thalassemia control group(--(SEA) /αα) in most hematological parameters (>0.05). The two-round nested PCR could effectively detect the HKαα/--(SEA) genotype. The hematologic characteristics changed significantly in HKαα/--(SEA) group compared with HbH thalassemia and normal group. The genotype and phenotype non-correlation in patients with α-thalassemia should especially be causious to avoid a misdiagnosis of genetic tests, especially in prenatal diagnosis.
分析α珠蛋白基因簇存在 -α(3.7,) --(SEA) 且α(2) 等位基因正常的地中海贫血样本中的基因型 - 表型相关性。纳入了2011年8月至2016年8月在本实验室16080名参与者中经血液学分析和基因检测疑似诊断的14例患者（包括1例胎儿，4例男性和9例女性，年龄0 - 56岁）。在XE4000i自动血细胞分析仪上进行全血细胞计数。采用高效液相色谱法（HPLC）检测HbA0、HbF和HbA2。采用缺口聚合酶链反应（Gap-PCR）检测三种常见缺失型地中海贫血缺失。应用反向点杂交（RDB）分析法检测17种常见β珠蛋白基因突变和三种常见非缺失型α(2) 基因突变。建立两轮巢式聚合酶链反应（PCR）检测α地中海贫血中HKαα的基因型。14例被鉴定为HKαα/--(SEA)（14/16080），包括一个家系以及1例HKαα/--(SEA) 与IVS-Ⅱ-654（C→T）杂合子共遗传的罕见病例。在HKαα/--(SEA) 地中海贫血组中，平均红细胞体积（MCV）为（69.54±5.92）fl，平均红细胞血红蛋白含量（MCH）为（22.11±2.22）pg，血红蛋白（Hb）为（117.64±18.14）g/L。与正常组相比，HKαα/--(SEA) 地中海贫血组的MCV、MCH和Hb显著降低（<0.05）。在大多数血液学参数方面，α地中海贫血对照组（--(SEA) /αα）之间无显著差异（>0.05）。两轮巢式PCR可有效检测HKαα/--(SEA) 基因型。与HbH地中海贫血组和正常组相比，HKαα/--(SEA) 组的血液学特征有显著变化。α地中海贫血患者的基因型和表型不相关，在基因检测中应特别谨慎以避免误诊，尤其是在产前诊断中。
