Two new human hemoglobin variants caused by unusual mutational events: Hb Zaïre contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain.
With rare exceptions, the more than 600 human hemoglobin variants described are caused by a single point mutation. Other abnormal features, such as unequal crossing-over, frameshift mutagenesis or double mutations in the same polypeptide chain, have seldom been encountered. We report two new variants caused by such rare mutational events. Hb Zaïre [alpha 116(GH4)-His-Leu-Pro-Ala-Glu-117 (GH5)] is the second example in which a short amino acid sequence is inserted within the alpha-chain. This abnormal hemoglobin results from a tandem repetition of 5 amino-acid residues, from sequence 112 through 116, at the end of the GH corner. Hb Duino is an unstable hemoglobin. It presents within the same beta-chain, the association of two rare point mutations; these substitutions are those found in Hb Newcastle [beta 92(F8)His----Pro] and in Hb Camperdown [beta 104(G6)Arg----Ser]. Family studies demonstrated that the Hb Newcastle abnormality was a de novo mutation of a gene already carrying the Hb Camperdown substitution.
Wajcman
H
H
INSERM U299, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Blouquit
Y
Y
Vasseur
C
C
Le Querrec
A
A
Laniece
M
M
Melevendi
C
C
Rasore
A
A
Galacteros
F
F
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
D006455:Hemoglobins, Abnormal; C076373:hemoglobin Duino; C076372:hemoglobin Zaire; C076371:hemoglobin Newcastle