广州地区1571例胎儿地中海贫血产前基因型与血液学特征分析

The analysis of prenatal thalassemia genetic diagnosis and hematologic characteristics of 1571 fetuses in Guangzhou area

目的：研究胎儿地中海贫血（地贫）的发生率及基因型分布，了解胎儿中、重型地贫的检出率，探讨地贫胎儿的血液学指标特点。方法：收集2011年8月到2015年8月在我院分子诊断室进行产前地贫基因检测的病例共1571例，其中根据孕周不同分为绒毛（9-11周）143例、羊水（16-20周）1064例和脐血（20-38周）364例。用XE4000i血细胞分析仪对脐血进行血液学指标（MCV、MCH、Hb）检测。用Gap—PCR技术检测缺失型α-地贫，反向斑点杂交技术（RDB—PCR）检测β-地贫和非缺失型地贫，可疑标本通过测序确定。结果：在1571例胎儿中，检测出正常胎儿621例（39．53％），异常胎儿950例（60．47％），其中α-地贫641例（40．80％），β-地贫258例（16．42％），α复合β地贫51例（3．25％）。检出中、重型α-地贫胎儿149例（9．48％），中、重型β-地贫胎儿44例（2．80％），总中、重型地贫的检出率高达12．29％。正常胎儿组的MCV为（113．25±9．20）fl，MCH为（37．71±2．70）Pg，Hb为（128．42±22．25）g／L，与正常胎儿组相比，α-地贫1纯合子组（-SEA／-SEA）、α-地贫1杂合子组（-SEA／αα）和HbH病的MCV、MCH、Hb明显降低（P〈0．05），静止型地贫组（-α3．7／αα、-α4．2／αα）和α复合β地贫的MCV、MCH明显降低（P〈0．05），非缺失型α-地贫组的MCH、Hb明显降低（P〈0．05），β-地贫各项血液学指标结果与正常对照组差异无统计学意义（P〉0．05）。结论：α-地贫胎儿血液学指征变化明显，而β-地贫在胎儿期表现隐匿，因此对胎儿进行产前地贫基因检测是非常有必要的，尤其双方都是同型α-地贫或β-地贫夫妇，这样可有效地预防中、重型地贫胎儿的出生，控制地贫的发生率。不同基因型的胎儿血液学指标有不同特点，检测胎儿血象对于患病胎儿的产前筛查及产前诊断有一定的补充意义。

Objective To in,：estigate the incidence and genotype disribution of thalassemia in fetuses, and study the detection rate of thalassemia major, and the relationship between the genotype and characteristics of fetal blood parameters. Methods 1571 participants underwent thalassemia genetic testing in laboratory of The First Affiliated Hospital of Sun Yat-Sen University from August 2011 to August 2015 are included in the research, including 143 villus samples, 1064 amniotic fluid samples and 364 fetal blood samples. Complete blood cell count and hemoglobin electrophoresis analysis were examined by XE4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography （HPLC）. Gap-PCR was adopted to detect three common deletional thalassemias deletion. Reverse dot-blot （RDB） assay was applied for detecting the three common nondeletional α2 gene mutations and β-thalassemias. The suspected subjects were determined by sequencing on ABI 3730XL. Results Overall, 621 fetus（39.53%） were normal, while 950 fetus （60.47%） were identified thalassemias, of which 641 were αlpha-thalassemia cases （40.8%）, 258 beta-thalassemia cases （16.42%）, and 51odpha- thalassemia compound with beta-thalassemia cases（3.25%）. -SEA deletion and-α3.7 were the most common αlpha- thalassemia genotypes , while CD41-42（-TCTr）, IVS-II-654 （C→T） and -28 （A→G） were the most common beta-thalassemia genotypes. 149 αlpha-thalassemia major cases （9.48%） were detected, and 44 beta-thalassemia major cases （2.80%）. The rate of thalassemia major was 12.29%. In normal fetus group, mean cell volume （MCV） was 113.25 ±9.20fl, and mean cell hemoglobin （MCH） was 37.71 ±2.70pg, and hemoglobin（Hb） was 128.42±22.25g/L, while in alphathalassemia group, MCV, MCH, Hb significantly decreased （P〈0.05） There were no significant differences between beta -thalassemia control group in most hematological parameters （P〉0.05）. Conclusion The hematologic characteristics changed significantly in alphathalassemia group compared with beta- -thalassemia in the fetal period. For the couple with the same type of alpha- thalassemia or beta - thalassemia, it is rather necessary to provide prenatal screening and diagnosis to decrease the incidence rate of thalassemia.