Hb Saint Nazaire (beta 103[G5]Phe-->Ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity.
Hb Saint Nazaire [beta 103 (G5) Phe-->Ile] was found in four apparently unrelated French families. The five patients carrying this hemoglobin have been detected because of a moderate erythrocytosis. The structural abnormality of Hb Saint Nazaire concerns the same residue as in Hb Heathrow [beta 103 (G5) Phe-->Leu). A comparative functional study between these two variants showed that the increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is localized within the heme pocket, by a leucine abolishes several contacts between the heme and the globin and leads to an environment of the heme having some similarities with that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications.
Wajcman
H
H
INSERM U299, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Kister
J
J
M'Rad
A
A
Promé
D
D
Milpied
N
N
Rapp
M J
MJ
Harousseau
J L
JL
Riou
J
J
Bardakdjian
J
J
Galacteros
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D014644:Genetic Variation / Q000235:genetics*; D006418:Heme / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000032:analysis*; D007930:Leucine / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010649:Phenylalanine / Q000032:analysis*; D011086:Polycythemia / Q000097:blood / Q000209:etiology* / Q000235:genetics*
D000596:Amino Acids; D006455:Hemoglobins, Abnormal; D007532:Isoleucine; C082452:hemoglobin Saint Nazaire; D006418:Heme; D010649:Phenylalanine; D007930:Leucine; D010100:Oxygen