Different Origin of nt 1246 Glucose-6-Phosphate

tient
4.4
values
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
CORRESPONDENCE
3592
Different Origin of nt 1246 Glucose-6-Phosphate Dehydrogenase Mutation
To the Editor:
we raise the question of
In view of this and other ob~ervations,~
whether it is worthwhile to continue to define G6PD variants by
names related to the origin of the subjects investigated or to define
them simply by the nt site of the molecular defect.
In a recent issue of Blood, Hirono et al' reported a molecular
study of 8 Japanese cases of glucose-6-phosphate dehydrogenase
(G6PD) deficiency. Among these cases, they found 2 subjects carrying a G A mutation at nt 1246 (exon 10) that has already been
described asbeing responsible for the G6PD Tokyo variant in a
single Japanese subject with hereditary nonspherocytic hemolytic
anemia.* They hypothesise that all the individuals bearing this mutation are descendants of the same individual, because they mention
that the G6PD Tokyo mutation has been found repeatedly only in
Japanese patients.
A mutation at nucleotide
We recently described the same G
position 1246 in a subject of Italian ancestry (as documented for at
least three generations) originating from Southern Italy. Nucleotide
sequencing also found a silent C --t T mutation at nt 131 1 responsible
for a polymorphic site common in Caucasian populations and rare
in oriental^.',^ These observations lead tothe conclusion that the
1246 G -+ A mutation inthe G6PD gene is present in different
populations and it has arisen independently in Japan and in Italy.
Our subject also had a chronic nonspherocytic hemolytic anemia;
however, it is noteworthy that the enzymologic properties of the
Italian and Japanese G6PD Tokyo are slightly different, mainly for
substrate analogues use (Table 1). Itwillbeof
interest toknow
whether the enzymes of Japanese subjects have the same kinetic
properties.
Because of the progresses in the molecular techniques applied to
the study of G6PD gene,' we can speculate that, in the near future,
several other molecular abnormalities will beidentified that are associated to different biochemical variants already named; on the other
hand, although rare, we can deal with new, unnamed G6PD-deficient
enzymes with different biochemical properties having a mutation
already attributed to a named variant, as is the case for our G6PD
variant.
M.D. Cappellini
F. Martinez di Montemuros
G. Fiorelli
Isrituto di Medicina Interna e Fisiopatologia Medica
IRCCS
Pad Lirta- University of Milan
Milnno, Italv
-+
"
+
REFERENCES
1. Hirono A, Miwa S, FujiiH, Ishida F, Yamada K, Kubota
K: Molecular study of eight Japanese cases of glucose-6-phosphate
dehydrogenase deficiency by nonradioisotopic single-strand conformation polymorphism analysis. Blood 83:3363, 1994
2. Hirono A, Fujii H, Hirono K, Kanno H, Miwa S: Molecular
abnormality of a Japanese glucose-6-phosphate dehydrogenase variant (G6PD Tokyo) associated with hereditary non-spherocytic hemolytic anemia. Hum Genet 88:347, 1992
3. Martinez di Montemuros F, Cappellini MD, Dotti C, Tavazzi
D, De Bellis G, Debernardi S, Fiorelli G: Molecular characterisation
of an Italian G6PD variant responsible for chronic non-spherocytic
haemolytic anaemia. Clin Genet 1994 (in press)
4. Beutler E, Kuhl W: The NT 1311 polymorphism of G6PD:
G6PD Mediterranean mutation may have originated independently
in Europe and Asia. Am J Hum Genet 47:1008, 1990
5 . Vulliamy T, Beutler E, Luzzatto L: Variants of glucose-6phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene. Hum Mutat 2:159, 1993
Table l.Biochemical Data
Analogues (% of use)
Activity (% of N)
Italian
GGPD Tokyo
50-70 Normal 100
Mobility (% of N)'
3.314
4.4
65
100
Mean data of three determinations are shown.
Mobility inTris-borate-EDTA (EBT) buffer.
93
4.2
90
K;''
(pmol/L)
K?DP (pnol/L)
GalGP
2dG6P
52
dNADP
16
5.5
14
-
47
55
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
1994 84: 3592-3594
Predicting complete cytogenetic response in chronic myelogenous
leukemia patients treated with recombinant interferon alpha [letter;
comment]
FX Mahon, M Montastruc, C Faberes and J Reiffers
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