Li Qiang, Li Li-Yan, Mo Qiu-Hua
Department of Medical Genetics, School of Basic Medical Sciences and Technology Center for Prenatal Diagnosis and DNA Testing of Genetic Disorders of Nanfang Hospital, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jan;28(1):16-9.
To analyze the relation between the genotype and phenotype in a Chinese patient with thalassemia intermedia and its implications for prenatal diagnosis and genetic counseling of thalassemia intermedia caused by co-existence of Hb H disease and beta; thalassemia major.
Phenotypic analysis was performed using standard hematological tests to measure red blood cell parameters and Hb concentration. Genotyping of beta thalassemia mutations and alpha thalassemia deletion were conducted using reverse dot-blot (RDB) assay and gap-PCR, respectively. We investigated the pathogenesis of this case by genotype-phenotype correlation analysis based on screening of the patient's family members. Prenatal diagnosis for a high-risk fetus in this family was performed by amniotic fluid DNA analysis.
The proband was identified as a patient with severe thalassemia intermedia caused by co-existence of Hb H disease (--(SEA)/-alpha (4.2)) and beta-thalassemia major (beta (CD17A)>T/beta (IVS2-654C)>T), whose father was heterozygous for beta thalassemia (beta (CD17A)>T/beta (N)) and alpha-thalassemia trait (--(SEA)/) and the heterozygous for beta thalassemia (beta (IVS2-654C)>T / beta (N)) and silent alpha-thalassemia (-alpha (4.2)/). The result of prenatal diagnosis showed co-existence of beta thalassemia major and silent alpha thalassemia in the high-risk fetus, and the parents requested termination of pregnancy after genetic counseling.
We report for the first time a rare thalassemia intermedia case resulting from 4 complex alpha/beta thalassemia combination and the molecular pathogenesis of thalassemia intermedia is updated in the Chinese population. The practice of prenatal diagnosis in this case may also provide reference for diagnosis of similar cases.
分析1例中间型地中海贫血中国患者的基因型与表型之间的关系，及其对由Hb H病和重型β地中海贫血共存所致中间型地中海贫血的产前诊断和遗传咨询的意义。
采用标准血液学检测进行表型分析，以测量红细胞参数和血红蛋白浓度。分别采用反向点杂交（RDB）法和缺口聚合酶链反应（gap-PCR）对β地中海贫血突变和α地中海贫血缺失进行基因分型。通过对患者家庭成员进行筛查，并基于基因型-表型相关性分析来研究该病例的发病机制。通过羊水DNA分析对该家庭中的高危胎儿进行产前诊断。
先证者被诊断为因Hb H病（--(SEA)/-α(4.2)）和重型β地中海贫血（β(CD17A)>T/β(IVS2-654C)>T）共存导致的重型中间型地中海贫血患者，其父亲为β地中海贫血杂合子（β(CD17A)>T/β(N)）和α地中海贫血特征（--(SEA)/），母亲为β地中海贫血杂合子（β(IVS2-654C)>T /β(N)）和静止型α地中海贫血（-α(4.2)/）。产前诊断结果显示高危胎儿存在重型β地中海贫血和静止型α地中海贫血共存的情况，在遗传咨询后父母要求终止妊娠。
我们首次报道了1例由4种复杂的α/β地中海贫血组合导致的罕见中间型地中海贫血病例，并且更新了中国人群中中间型地中海贫血的分子发病机制。该病例的产前诊断实践也可为类似病例的诊断提供参考。
