Haemoglobin Hokusetsu [beta52 (D3)] Asp-->Gly in German families associated with inclusion body.
Inclusion bodies associated with Hb Hokusetsu have never been published. We investigated the autoxidation of this variant as a cause for the inclusion bodies in three unrelated families. Moreover, haplotype analysis was carried out to unravel the origin of this variant also found in the Japanese population. The presence of inclusion bodies was revealed by incubating the fresh peripheral blood with brilliant cresyl blue. We further characterised this variant using mass spectrometry and DNA analysis. The generation of superoxide radical (ROS) during the autoxidation was assayed by electron spin resonance spectrometry. Inclusion bodies were seen in about 25% of red cells. Hb Hokusetsu turned out to be less thermostable than the control. It showed a tenfold-enhanced ROS formation versus control. The analysis of the beta-globin haplotypes for the three unrelated families showed that Hb Hokosetsu was linked with haplotype I (5' + - - - - + + 3'). This is the first case published in the German population. The inclusion bodies could be due to the instability of the variant. This is supported by the increased autoxidation. The absence of anaemia evokes an elimination of the inclusion bodies by the proteolytic mechanism of the red cells. The association of the variant in three unrelated families with the five polymorphisms of haplotype I indicates a single common mutation event. In the presence of Hb Hokusetsu, HbA 1C standard methods used to assess glycaemic control are mistaken.
Bissé
Emmanuel
E
Department of Clinical Chemistry, University Medical Center, Hugstetterstrasse 55, 79106 Freiburg, Germany. bisse@med1.ukl.uni-freiburg.de
Zorn
Nathalie
N
Preisler-Adams
Sabine
S
Epting
Thomas
T
Sommer
Olaf
O
Schaeffer
Christine
C
Van Dorsselaer
Alain
A
Horst
Jürgen
J
Wieland
Heinrich
H
D019943:Amino Acid Substitution; D001224:Aspartic Acid; D017931:DNA Primers; D005190:Family; D005260:Female; D014644:Genetic Variation; D005858:Germany; D005914:Globins / Q000235:genetics; D005998:Glycine; D006454:Hemoglobins / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male
D017931:DNA Primers; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; C116243:hemoglobin Hokusetsu; D001224:Aspartic Acid; D005914:Globins; D005998:Glycine