A new Hb evanston allele [alpha14(A12)Trp --> Arg] found solely, and in the presence of common alpha-thalassemia deletions, in three independent Asian cases.
Hb Evanston [alpha14(A12)Trp --> Arg] is considered to be a rare alpha chain mutant, and was originally observed in two Black families in 1982, inducing a mild Hb H disease phenotype in a homozygous state for the -alpha3.7 deletion ( -alpha(Evanston)/ -alpha). The mutant, evidently linked with one of the two -alpha3.7 thalassemia (thal) alleles, was considered to be unstable and rapidly proteolyzed. We describe Hb Evanston in three new independent Asian cases, all induced by a TGG --> CGG transition. In all cases the mutation is linked to the alpha1-globin gene, either on a wild type allele or in linkage with the common -alpha3.7 and -alpha4.2 deletion alleles. The beta/alpha ratio was balanced in the presence of the mutation only, and accordingly unbalanced in co-inheritance with the deletion defects. Although a second independent mutation event on a -alpha3.7 or a -alpha4.2 deletion allele could not be excluded, we conclude that at least one independent Hb Evanston mutation has occurred on a wild type allele in the Asian populations. Unstable Hb tetramers tend to degrade and disappear during purification. Both Hb Evanston tetramers, formed in combination with normal beta and delta chains, remain perfectly stable after extensive purification and concentration steps, suggesting an early posttranslational thalassemic effect, probably at the dimer/tetramer affinity level.
Harteveld
Cornelis L
CL
Department of Human and Clinical Genetics and The Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
Wijermans
Pierre W
PW
de Ree
Juliette E L M
JE
Ter Hal
Pauline
P
Van Delft
Peter
P
Van Rooijen-Nijdam
Irene H
IH
Rasp
Ellen
E
Kok
Peter J M J
PJ
Souverijn
John H M
JH
Versteegh
Florens G A
FG
Giordano
Piero C
PC
D000328:Adult; D000346:Afghanistan; D000483:Alleles; D019943:Amino Acid Substitution; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000235:genetics*
D006455:Hemoglobins, Abnormal; C039216:hemoglobin Evanston