摘要
目的分析同时出现正常条带α2、右缺失（－α3.7）和东南亚缺失（－－SEA）患者基因型和血液学的关系，为临床诊断和遗传咨询提供指导。方法回顾性分析2011年8月至2016年8月来中山大学附属第一医院分子诊断室进行地贫基因检测的16 080例患者的临床资料，挑选出同时出现正常条带α2、右缺失（－α3.7）和东南亚缺失（－－SEA）的患者14例（男4例，女9例，胎儿1例）。用XE 4000i血细胞分析仪进行血细胞分析，采用高效液相色谱法（HPLC）定量检测血红蛋白A0（HbA0）、血红蛋白A2（HbA2）和血红蛋白F（HbF），用跨越断裂点多聚酶链反应（Gap－PCR）技术检测常见的3种缺失型α－地贫，并用反向斑点杂交技术检测17种常见的β－地贫和3种常见的非缺失型α－地贫基因。用两轮巢氏PCR检测HKαα型α－珠蛋白生成性贫血。结果16 080份样本中，共检测出HKαα合并东南亚型缺失14例（HKαα/－－SEA），检出率为0.087%，且存在1个HKαα/－－SEA家系，发现其中1例为罕见的HKαα/－－SEA合并βIVS－Ⅱ－654/βN胎儿病例。HKαα/－－SEA组的平均红细胞体积（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组的MCV、MCH、Hb明显降低（P〈0.05）；与α－地贫杂合子组（－－SEA/αα）相比，MCH、Hb值差异无统计学意义（P〉0.05）；与血红蛋白H（HbH）病（－α3.7/－－SEA）组比，HKαα/－－SEA组的MCV、MCH、Hb明显较高，差异有统计学意义（P〈0.05）。结论两轮巢式PCR可鉴定HKαα/－－SEA，血液学主要表现为小细胞低色素性贫血，与－－SEA /αα表型类似，但比HbH病轻，能够给临床提供准确的产前诊断和遗传咨询策略。
ObjectiveTo analyze the genotype-phenotype correlations among those thalassemia samples with the presence of -α3.7, --SEA and normal α2 alleles on their α-globin gene clusters.MethodsFourteen 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 α2 gene mutations. Two-round nested PCR assay was established to detect the genotype of HKαα in α-thalassemia.ResultsFourteen 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（P〈0.05）. There were no significant differences between α-thalassemia control group（--SEA /αα） in most hematological parameters （P〉0.05）.ConclusionThe 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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2018年第2期117-121,共5页
National Medical Journal of China
