thalassemia Watson Crick 1953 neucleic acid 3 10 9 46 mitochondria Mckusick 2208 2136 4344 1988 2208 1433
626 139 genotype phenotype
peptide chain 1 2 2 HbA 2 HbA2 thalassemia (1) (2) (3) (4) MCV mean corpuscular vol-ume H 4 HbH hydrops fetalis 4 Hb Bart s Hb Bart s hydrops fetalis deletion
thalassemia major 1/4 17 4 90% 1% 3% 2%
15% 1% 2% 80 HbA 2 4 HbF 1/4 16 17 Hb bart s
-24-2002 -thalassemia -globin -globin -globin -globin -globin -thalassemia-2 -globin -thalassemia-1 HbH -globin -globin tetramer( 4) HbH -thalassemia major -thalassemia (deletion) -thalassemia-2-3.7, - 4.2, - 2.7, - 5.3, - 3.5 HbCS Hb -thalassemia-1 ( / ) (homozygous) -thalassemia-2 ( / ) / -thalassemia major ( / ) HbH / cs / -thalassemia -thalassemia -globin -globin 11 -globin -globin -globin -globin / / -globin -thalassemia major -thalassemia major -globin -thalassemia major 3~6
-thalassemia-2 1~3% -thalassemia-1 5% -thalassemia-2-4.2, - 3.5 HbCS -thalassemia-1 SEA 17kb 1, 2 PHIL THAI SEA 1, 2 - HbH / T T HbCS -thalassemia major SEA / SEA ( )
-thalassemia-1
-thalassemia-2 -thalassemia 1~2% (>90%) 28(A G), codon 17(AAG TAG), codon 41/42( TCTT), IVS-2 nt 654(C T) 32(C A), 30(T A), 29(A G), AAAC( 40 to 43 from cap), initial codon (ATG AGG), codon 14/15 ( G), codon 27/28 ( C), IVS-1 nt 1 (G T), IVS-1 nt S(G C), IVS-1 3' end (TAG GAG), codon 43 (GAG TAG), codon 71( T), codon 71/72 ( A) 32, 30, 29, 28 promoter exon intron IVS-1 nt1, IVS-1 nt5, IVS-1 3' end, IVS-2 nt 654 (IVS intervening sequence, intron) mrna splicing CBC - -thalassemia - -thalassemia MCV MCH (MCV< 80 MCH< 25) -thalassemia HbA2 HbF (HbA2>4.0 HbF>2.0) -thalassemia 1. MCV, MCH
2. HbA2 HbF HbA2 3~4 - -thalassemia HbE Hb variants HbA2 3. HbA2 HbF -thalassemia 5% -thalassemia 4. -thalassemia -thalassemia MCV MCH 5. CBC HPLC MCV 80 MCH 25 Ferritin HbA2 4.0 HbA2 3 4.0 HbA2 3.0 DNA -and -thalassemia DNA --thalathalassemia HbA2 DNA -and
-thalassemia Southern blot PCR PCR homozygous deletion deletion junction DNA double check-up Southern blot -thalassemia-2 -thalassemia-1 -thalassemia ASO(Allele-Specific Oligonucleotide), ARMS(Amplification Refractory Mutation System), PCR sequencing ACRS(Amplification Created Restriction Sites) sequencing -thalassemia HbH HbH genotype phenotype genotype ( ) HbH ( -thalassemia major ) -thalassemia -thalassemia intermedia -thalassemia major HbH -thalassemia intermedia -globin -globin ( 0 / ) HbH ( / ) -thalassemia intermedia -thalassemia intermedia HbH
( ) normal control, homozygous mutation control, heterozygous mutation control blank control