HB Gouda [alpha 72(EF1)His-->Gln], a new silent alpha chain variant.
We describe a new alpha chain mutant accidentally found in a diabetic patient. The propositus is being treated for diabetes mellitus II with 4% glycated hemoglobin (Hb A1C). The variant, named Hb Gouda, is not detectable by starch gel electrophoresis but appears as a shoulder before the Hb A fraction during the chromatographic separation of Hb A1C. The hematological analysis revealed normal parameters with a normal serum iron value. No anomalies were reported in connection with Hb Gouda. The tryptic peptide map and sequencing of the alpha T-9 peptide revealed the substitution of a histidine by a glutamine at position 72. By selective amplification and sequencing of both the alpha genes, we have assigned the new mutation to the alpha 2 gene. Position 72 of the alpha chain is a moderately conserved site located between two non-conserved amino acids. This site is not involved in heme, dimer or tetramer contacts, or in Bohr effect or in 2,3-diphosphoglycerate binding.
Giordano
P C
PC
Institute of Human Genetics, State University of Leiden, Netherlands.
Harteveld
C L
CL
Kok
P J
PJ
Geenen
A
A
Batelaan
D
D
Amons
R
R
Bemini
L F
LF
D000595:Amino Acid Sequence; D001483:Base Sequence; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D005914:Globins / Q000235:genetics*; D005973:Glutamine / Q000737:chemistry*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
D006455:Hemoglobins, Abnormal; C103887:hemoglobin Gouda; D005973:Glutamine; D006639:Histidine; D005914:Globins