Hb M Dothan [beta 25/26 (B7/B8)/(GGT/GAG-->GAG//Gly/Glu-->Glu]; a new mechanism of unstable methemoglobin variant and molecular characteristics.
A new unstable beta globin chain variant associated with methemoglobin (Met-Hb) phenotype was found in a Caucasian infant. Molecular analysis of the beta globin gene using polymerase chain reaction (PCR) amplification and sequencing led to the detection of a new in frame deletion in exon-1. Direct sequencing of the PCR product revealed a 3 bp deletion (-GTG) between codons 25/26, which resulted in the loss of a single amino acid (-Gly). We propose that this newly discovered unstable M-hemoglobin (M-Hb) variant, named Hb Dothan [GGT/GAG-->GAG//Gly/Glu-->Glu], is caused by a shift in the amino acid sequence and altered packing of the B and E helices during beta globin synthesis, and also changes the orientation of the critical proximal and distal histidine in the F and E helices respectively. Phenotype/Genotype features and molecular characteristics of this new beta chain are presented in this communication.
Kutlar
F
F
Sickle Cell Center, Medical College of Georgia, Augusta, GA 30912, USA. fkutlar@mcg.edu
Hilliard
L M
LM
Zhuang
L
L
Patel
N
N
Eroglu
B
B
Meiler
S E
SE
Carmichael
H
H
Russell
R B
RB
Kutlar
A
A
D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008706:Methemoglobin / Q000737:chemistry / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D017384:Sequence Deletion; D055544:beta-Globins / Q000235:genetics*
D055544:beta-Globins; D008706:Methemoglobin