[A rare thalassemia intermedia case caused by co-existence of Hb H disease (--(SEA)/-alpha(4.2)) and beta-thalassemia major (beta (CD17A)>T/beta (IVS2-654C)>T): implications for prenatal diagnosis].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Qiang
Q
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. liq@fimmu.com
Li
Li-Yan
LY
Mo
Qiu-Hua
QH
D000328:Adult; D002675:Child, Preschool; D002681:China; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D017085:alpha-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D017086:beta-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*