Document Detail

Prenatal diagnosis of beta-thalassemia major by high-performance liquid chromatography analysis of hemoglobins in fetal blood samples.
MedLine Citation:
PMID:  11300346     Owner:  NLM     Status:  MEDLINE    
In Thailand and adjacent countries, most of the beta-thalassemia genes are beta(0)-thalassemia mutations that prevent the production of Hb A. We propose the quantitation of the Hb A fraction in fetal blood in the mid-trimester of pregnancy by automated high performance liquid chromatography as a reasonable prenatal diagnostic method to be applied in areas with limited laboratory facilities. Forty pregnant women at risk of delivering a child with beta-thalassemia major were identified using an erythrocyte osmotic fragility test and quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18-22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high performance liquid chromatography. The beta-globin gene mutations were characterized by beta-globin gene sequencing. The 4 bp deletion at codons 41/42 (-TTCT) was the most frequent of the 40 beta-thalassemia mutations observed (20/40 = 50%), followed by the splice site mutation IVS-I-1 (G-->T) (7/40 = 17.5%), the nonsense mutation at codon 17 (A-->T) (7/40 = 17.5%), the nonsense mutation at codon 35 (C-->A) (3/40 = 7.5%), and the beta(+)-thalassemia promoter mutation at -28 (A-->G) (3/40 = 7.5%). High performance liquid chromatography revealed nine fetuses which had only Hb F and no Hb A. All were homozygotes or compound heterozygotes for beta(0)-thalassemia mutations. In the remaining 31 fetuses, a Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a compound heterozygote for the -28 (A-->G) and codons 41/42 (-TTCT) mutations. In the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of these, with a Hb A concentration of 1.82 +/- 0.49% (range 0.8-2.8%), were beta-thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 +/- 1.47% (range 2.9-7.4%) and normal beta-globin genes. The absence of Hb A in homozygotes or compound heterozygotes for beta(0)-thalassemia mutations and the presence of measurable amounts of Hb A in heterozygotes and normal homozygotes, permits the diagnosis of fetuses expected to develop postnatal beta-thalassemia major.
T Sanguansermsri; P Thanarattanakorn; H F Steger; T Tongsong; P Chanprapaph; C Wanpirak; P Siriwatanapa; S Sirichotiyakul; G Flatz
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Publication Detail:
Type:  Evaluation Studies; Journal Article    
Journal Detail:
Title:  Hemoglobin     Volume:  25     ISSN:  0363-0269     ISO Abbreviation:  Hemoglobin     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-09-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7705865     Medline TA:  Hemoglobin     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-27     Citation Subset:  IM    
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Thailand.
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MeSH Terms
Chromatography, High Pressure Liquid*
Codon / genetics
Codon, Nonsense
DNA Mutational Analysis
Fetal Blood / chemistry*
Fetal Diseases / blood,  diagnosis*
Gestational Age
Globins / genetics*
Hemoglobins, Abnormal / analysis*
Polymerase Chain Reaction
Prenatal Diagnosis / methods*
Promoter Regions, Genetic / genetics
Prospective Studies
Sequence Deletion
Specimen Handling
beta-Thalassemia / blood,  diagnosis*,  embryology
Reg. No./Substance:
0/Codon; 0/Codon, Nonsense; 0/Hemoglobins, Abnormal; 9004-22-2/Globins

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