Hb Bleuland [alpha108(G15)Thr-->Asn, ACC-->AAC (alpha2)]: a new abnormal hemoglobin associated with a mild alpha-thalassemia phenotype.
We report a new structural defect of the alpha2-globin chain, not detectable on high performance liquid chromatography (HPLC) or electrophoresis, characterized in a 12-year-old boy of Surinamese-Hindustani origin. The child was suspected to be a carrier of alpha-thalassemia (thal) because of microcytic hypochromic parameters in the absence of iron depletion. Gap-polymerase chain reaction (gap-PCR) revealed only normal fragments in the proband, and the pattern of a -alpha4.2 (leftward) deletion in his father and sister. Direct sequencing of the alpha-globin genes revealed an ACC-->AAC transversion at codon 108 of the alpha2-globin gene in the proband, in his mother and in a younger sister. The new mutation predicts a Thr -->Asn amino acid substitution at the corresponding residue. Threonine, a covalent binder with an R-active OH group, situated in the G helix of the alpha-globin chain, is involved in alpha1beta1 contacts. Asparagine, being an equally covalent binder but with a different R-active H2N-C=O group, could make the mutated chain less suitable for tetramer cooperation. Alternatively, an absent or reduced interaction with the alpha hemoglobin (Hb) stabilizing protein (AHSP) could lead to loss of alpha chains. Hb Bleuland is the first mutation described at codon 108 and is therefore interesting in regard to the possible effects and genetic risk. The nearest variant, Hb Suan-Dok [alpha109(G16)Leu -->Arg, CTG-->CGG (alpha2)] was originally observed in a Thai patient affected with Hb H, in combination with an alpha0-thal allele. The same Hb Suan-Dok mutation, recently described in our laboratory in a carrier of African ancestry, was also not detectable as a protein and presented with an alpha-thal phenotype similar to Hb Bleuland.
Harteveld
Cornelis L
CL
The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Versteegh
Florens G A
FG
Kok
Peter J M J
PJ
van Rooijen-Nijdam
Irene H
IH
van Delft
Peter
P
Giordano
Piero C
PC
D000293:Adolescent; D000328:Adult; D001797:Blood Protein Electrophoresis / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D005914:Globins