Hb S-β-thalassemia: molecular, hematological and clinical comparisons.
Clinical and hematological features are presented for 261 patients with identified β-thalassemia (β-thal) mutations. Mutations causing Hb S [β6(A3)Glu→Val]-β(0)-thal were IVS-II-849 (A>G) in 44%, frameshift codon (FSC) 6 (-A) in 14%, Hb Monroe [β30(B12)Arg→Thr] in 14%, and IVS-II-1 (G>A) in 10%. Mutations causing Hb S-β(+)-thal with 14-25% Hb A (type III) were -29 (A>G) mutation in 60%, -88 (C>T) in 22% and the polyadenylation signal site (polyA) (T>C) mutation in 14%, and in Hb S-β(+)-thal with 1-7% Hb A (type I), all had the IVS-I-5 (G>C) mutation. Hematologically, only minor differences occurred between the four Hb S-β(0)-thal mutations, but among the three mutations causing Hb S-β(+)-thal type III, levels of Hb A(2), Hb F, hemoglobin (Hb), MCV and MCH were highest in the -88 and lowest in the polyA mutations. Clinically, Hb S-β(0)-thal and Hb S-β(+)-thal type I were generally severe, and Hb S-β(+)-thal type III disease with the -88 mutation was milder than that caused by the polyA mutation.
Medical Research Council Laboratories, Kingston, Jamaica. grserjeant@cwjamaica.com
Graham R
GR
Serjeant
Beryl E
BE
Serjeant
Raphael A
RA
Fraser
Ian R
IR
Hambleton
Douglas R
DR
Higgs
Andreas E
AE
Kulozik
Alan
A
Donaldson
D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D002648:Child; D003062:Codon; D005319:Fetal Hemoglobin / Q000235:genetics; D056726:Genetic Association Studies; D006403:Hematologic Tests; D006443:Hemoglobin A2 / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015997:Neonatal Screening; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D017086:beta-Thalassemia / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology
D003062:Codon; D006455:Hemoglobins, Abnormal; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin