1. No category

From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
Molecular Defect of a Phosphoglycerate Kinase Variant (PGK-Matsue)
Associated With Hemolytic Anemia: Leu +. Pro Substitution Caused by
T/A -+ C/G Transition in Exon 3
By Masato Maeda and Akira Yoshida
We have identified the mutation in a phosphoglycerate
kinase variant (PGK-Matsue) associated with severe enzyme
deficiency, congenital nonspherocytichemolytic anemia, and
mental disorders. The mRNA coding for PGK was reverse
transcribed and amplified by the polymerase chain reaction.
Nucleotide sequencing of the variant cDNA showed a point
mutation, a TIA + CIG transition in exon 3 of the variant
gene. No other mutation was found in all coding regions of
PGK-Matsue. The nucleotide change created an additional
NcA cleavage site in the variant gene; thus, the Ncil fragment
types detected by Southern blot hybridization differ in the
variant DNA and normal DNA. The mutation should cause
Leu + Pro substitution at the 88th position from the NH,terminal Ser of PGK. Because the Leu + Pro substitution is
expected to induce serious perturbationand instability in the
protein structure, the severe enzyme deficiency is mainly
caused by more rapid in vivo denaturation and degradation
of the variant enzyme.
o 1991 by TheAmerican Society of Hematology.
P
Amplification of mRNA. About 5 x lo7 fibroblast cells of
passages 17 and 26 were harvested from GM00743 and 9024,
respectively. Total cellular RNA samples were prepared from the
cells by extraction with guanidine thiocyanate followed by density
gradient centrifugation in cesium chloride.” The entire coding
sequences of mRNA were reverse transcripted and amplified in six
overlapped segments, using six sets of sense (A-1, B-1, . . . F-1) and
antisense (A-2, B-2, . . . F-2) oligonucleotide primers (Table 1).To
create adequate restriction sites, linker sequences were attached to
the 5‘ end of these primers (Table 1).
The first-strand cDNA copies of mRNA were produced by
incubating total RNA (8 to 10 Fg) with one of the antisense
primers (A-2, B-2,. . . F-2; 10 pmol) and 20 U of reverse transcriptase from avian myeloblastosis virus (Life Science, St Petersburg, FL) in the reaction mixture (20 FL) as described previously.”
The reaction products were amplified by the polymerase chain
reaction (PCR)’* using a corresponding set of sense and antisense
primers (50 pmol each) in the reaction mixture (100 pL) containing
20 m m o K Tris-HC1 (pH 8.3), 3.1 mmol/L MgCI,, 80 pmoUL D l T ,
58 mmoUL KCI, 0.01% gelatin, dNTP (200 pmoVL each), and 5 U
of Taq polymerase (Perkin-Elmer Cetus, Norwalk, CT). The
reaction was performed with a programmable thermal controller
(MJ Research, Inc, Watertown, MA). The cycle, which consisted of
1 minute of denaturation at 94T, 2 minutes of annealing at 50”C,
and 3 minutes of elongation at 72”C, was repeated for 40 times and
followed by another 12 minutes of elongation at 72°C.
To verify the amplification products, 1/20 of each reaction
mixture was separated by agarose gel electrophoresis, transferred
onto nitrocellulose filters, and hybridized with a ’*P-labeled fulllength human PGK cDNA (1.8 Kb BamHIIXho I insert of PGK 825
clone)” in 50% formamide (vol/vol), 5X Denhardt’s solution, 0.5%
sodium dodecyl sulfate, and 100 pg/mL salmon sperm DNA at
42°C.
Subcloning and sequencing of amplified DNA. The amplified
DNAs were digested with appropriate restriction enzymes, whose
recognition sites were created by PCR, and purified by electrophoresis in polyacrylamide gel followed by electro-elution. The purified
DNAs were subcloned into the M13 vector as described.” DNA
sequencing was performed by the dideoxy-nucleotide chain termination method of Sanger et al.l4To avert possible errors in the Taq
polymerase reaction, DNA fragments isolated from at least two
separate amplification reactions were sequenced in both orientations.
Restriction-fiagment analysis. Genomic DNAs were prepared
from GM00743 and 9024 fibroblast cells as described.” The DNA
samples (approximately 1 p,g each) were amplified using a pair of
primers, 5’-GCCAAGTCGGTAGTCClTATG-3’
and 5’-CGCCACAAAGTCTACCAGCAC-3‘, by PCR. The primers used corre-
HOSPHOGLYCERATE kinase (ATP: 3-phosphoglycerate 1-phosphotransferase, EC 2.7.3.3 [PGKJ) plays
a key role for ATP generation in the glycolytic pathway.
The PGK, which exists universally in various tissues of
various organisms, is encoded by a single structural gene on
the X-chromosome q13 in humans.’,*The complete amino
acid sequence, cDNA sequence, and genomic organization
have been el~cidated.~.’
An inherited deficiency of this
enzyme is associated with chronic nonspherocytic hemolytic
anemia and mental disordem6 Occasionally, the sole clinical manifestation has been muscle disease.’ The patient
with PGK-Matsue also had severe chronic hemolytic anemia and mental disorders: The activities of the enzyme in
red blood cells (RBCs), muscles, and fibroblasts of the
patient were about 5% of those of normal tissues? However, the content of mRNA in the patient’s fibroblasts was
comparable with that of normal fibroblasts.”’ We determined the nucleotide sequence of the variant cDNA to
elucidate the molecular abnormality of PGK-Matsue.
MATERIALS AND METHODS
Cell lines. The fibroblast cell line from the PGK-Matsue male
subject (identification GM00743) was obtained from the NIGMS
Human Genetic Mutant Cell Repository (Camden, NJ). A normal
fibroblast cell line of human newborn foreskin (9024) was obtained
from the cytogenetics laboratory, City of Hope National Medical
Center (Duarte, CA). The fibroblast cells were cultured in MEM
medium supplemented with 20% (volhrol)fetal calf serum (GIBCO,
Grand Island, NY), 24 mmol/L sodium bicarbonate, penicillin (50
UlmL), and streptomycin (50 mg/mL) at 37°C in 5% C0,/95% air.
From the Department of Biochemical Genetics, Beckman Research
Institute of the City of Hope, Duarte, CA.
Submitted July 5,1990; accepted November 6,1990.
Supported by US Public Health Service Grant HL-29515.
Address reprint requests to Akira Yoshida, PhD, Department of
Biochemical Genetics, Beckman Research Institute of the City of
Hope, 1450 E Duarte Rd, Duarie, CA 91010.
The publication costs of this article were defiayed in part by page
charge payment. This article must therefore be hereby marked
“advertisement” in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
0 1991 by The American Society of Hematology.
0006-4971I91/7706~OO12$3.00/0
1348
Blood, Vol77, No 6 (March 15). 1991: pp 1348-1352
From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
PHOSPHOGLYCERATEKINASE VARIANT (PGK-MATSUE)
1349
Remriction
Ses-
OliiOnUClaolide
A- 1
A-2
B-1
8-2
1.)
Site
sst1
(-51) 5'-GCgagCTCGlTGACCGAATCACCGA-3'(-27)
(287) 5'-AActgCAGAACATCCl-TGCCCAGCAG-3' (262)
(224) 5'-AGggaTCClTAGAGCCAGlTGCTGT-3' (248)
(557) 5'-CCAmCTGTGGCAGATTGACTCC-3' (532)
(450) 5'-CCaAGClTCACllTCCAAGCTAGGG-3' (474)
(776) 5'-TCclgCAGAGAAGTGCCAATCTCCA-3'(752)
(648)5'-AGcTGCAGACAAGATCCAGCTCAT-3' (671)
(1001) 5-ATaaGClTAGCCCGAGTGACAGCC-3' (978)
(955) 5'-GAcIGCAGCAAGAAGTATGCTG-3' (976)
(1188)
(1208) 5'-AGGAGCTCCAAACTGGCACCA-3'
(1116) 5'-TGGmACACTGCCAClTGCTGTG-3' (1141)
(1374) 5'-GCAaagClTGGCCACTAGCTGAATC-3' (1350)
c-1
c-2
D-1
D2
E-1
E-2
F-1
F-2
OligonucleotidesA-1, B-1, . ..F-1correspond to the sense strand of DNA. OligonucleotidesA-2,B-2,
DNA. Lowercaseletterswere altered to create corresponding restrictionsites (underlined).
'Counting from the adenine residue of the initiation codon.
-
spond to a 5' part of exon 3 (nucleotides 163
183, counting from
the adenine residue of the initiation codon of cDNA) and a 5' part
of intron 3 (nucleotides 18 + 38. counting from the intron-exon
junction). Therefore, the amplified product of 148 bp should
contain the mutation site.
Half of the amplified products produced from the control and
variant DNAs were digested by Ncil (IO U, Stratagene, La Jolla,
CA). The digested and undigested samples were electrophoresed
on 4% agarose gel in the Tris-Acetate-EDTA buffer system,
blotted onto nylon membranes, and hybridized with a PGK cDNA
probe ("P-laheled cDNA fragment produced by oligonucleotide
primers R-l and R-2).
RESULTS
Flg 1. Partial nud.atid. soquem of n o m 1 and vahnt
PGK-Matsue. The coding sequence h shown aligned with
the sequence ladders. Astdslts
indicate the substitution she of
the PGK-Matsue gene. The encoded amino acid residues are
shown. Numerals correspond t o
the residue number, counted
from the NH,-terrnlnal of the enzyme protein.
LeU
Leu
Set
PstI
Hindlll
PstI
sst I
Xb8 I
Hindlll
. . .F-2correspond to the antisense strand of
T
-c -G
a
T C G A
I I,
t ] Lys
LYS
GlY
PSf I
Nucleotide sequence analysis of these amplification products originating from PGK-Matsuc RNA showed only one
nucleotidc differcnce bctwccn thc variant PGK and the
rcportcd sequcncc of normal PGK.' A part of the nuclcotidc scqucncc ladders of PGK-Matsuc and thc normal
PGK is shown in Fig 1. A thymidinc rcsiduc at position 266
(counting from thc adeninc rcsiduc of thc initiation codon
of mRNA) in thc normal PGK was found to be substitutcd
by a cytidine rcsiduc in PGK-Matsue. Based on thc information of the genomic structure of thc PGK locus,' the
mutation site is located in exon 3. Thc nuclcotidc substitution is expected to gcncratc a new NciI (and isoschismatic
Ahol, Rcnl. Hpoll, Msp I) cleavage site, CCGGG, in thc
PGK-Matsuc gcnc. Thc 148-bp mutation region originating
from thc variant gcnc was in fact clcavcd by M i l , hut thc
corresponding region originating from thc normal gene was
not clcaved (Fig 2).
Thc transition T/A + C/G in thc gcnc should result in
Amplification of total cellular RNA by PCR using six sets
of sense and antisense oligonuclcotide primers (Table 1)
produccd six overlapping cDNA fragments, which were
hybridizablc with thc PGK cDNA prohc and m c r c d entire
coding scqucnccs.
(3')
PstI
88mHl
EcoRl
Hindlll
c!*
-
G
Gly
PI
Leu
T
Set
\ :j
(5')
From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
MAEDA AND YOSHIDA
1350
A
B
the amino acid substitution Leu (codon CTG in the normal
PGK) + Pro (codon CCG in PGK-Matsuc) at the 88th
position from thc NH,-terminal Scr residuc.
DISCUSSION
309217-
110-
1
1
2
2
Fig2 ~ b b t h y b r M i t r t k n o f P c R p r o d u c t r o f t h . n o m u l
and WK-Motsw DNAs. The 148-bp g ” k region, whkh includes
the mutation site, was ampllf’ied by the use of a pair of 5 and 3’
primers. Hall of the ampllf’ied product was dlgostd by NcA. Undigested and digested PCR products wow subjected to agarose gel
electrophomsis, and Southem blot hybridization using cDNA as a
hybridiratlon probe. (A) Undigested PCR product. Lane 1. product
from normal DNA; lane 2. product from PGK-Matsue DNA. (E) PCR
product digested by Ncil. Lane 1, normal DNA; lane 2. P G K - M m e
DNA. The left-hand column indicates the position of sire markers.
Note that a small fragment (44 bp), generated from PGK-Matsue DNA
by Ncil digestion, cannot be hybridizedwith the cDNA probe because
the fragment consists mostly of an Intron sequence and contrlns a
coding sequence of only 6 bp.
Chronic hcmolytic ancmia associated with RBC PGK
deficiency was first obscrvcd by Kraus et all5 in a fcmalc
paticnt. Subsequently, in their study of an unrelated large
family, Valcntinc et all found that the cnzyme dcficicncy
and clinical symptoms wcrc more sevcrc in malc than
fcmalc mcmbcrs. and suggcstcd thc Xchromosomc linkcd
inhcritancc of P G K dcficicncy. In addition to hcmolytic
ancmia, behavioral and ncurologic abnormalitics wcrc
obscrvcd in ccrtain affcctcd mcmbcrs of this family. At this
timc, 14 rare P G K variants associatcd with cnzyme dcficicncy have becn found in unrclatcd familics (Table 2). The
RBC enzyme activity in affcctcd malcs ranged from 3% to
20% of thc normal lcvcl. Thc dcficicncy was obscrvcd also
in nucleated tissucs, such as thc lcukocytcs and muscles of
the subjccts. Exccpt for PGK-Mhnchcn, which cxhibits
rclativcly mild dcficicncy (about 20% of the normal Icvcl),
all dcficicnt variants arc associated with chronic nonsphcrocytic hcmolytic ancmia, mcntal disorders, or rhabdomyolysis.
In addition to thcsc rare deficient variants, sevcral
electrophoretic variants with normal cnzymc activity have
bccn found in certain populations.’.”
The molecular abnormalitics of three deficient variants,
ic, PGK-Munchen,” PGK-Uppsala,” and PGK-Tokyo,”
and an clcctrophoretic variant, PGK-II,’D which is common
among Southcrn Pacific populations, were prcviously clucidatcd by thc pcptidc mapping analysis (Tablc 2). The
impact of thcsc structural abnormalitics on P G K function
has becn p r c d i ~ t c d ” . ’bascd
~ ~ ~ on thc thrcc-dimcnsional
structurc of horsc PGK,= which is highly analogous (about
97% scqucncc identity) to thc human cnzymc.
Clinicel Manifatstions
EruymsRopartier
invatwwms(-e
Kraus et al.”
Valentine et a.i‘
Hjelm et al.’Lnn
A r m et al.”
Canier et aI.=
Miwa et al.Konrad et al.”
Akatsub et a1.IBoivin et 0 1 . ~
Krietsch et al.””
Rosa et el.’
DiMauro et (11.Sugie et ai.=
Guis et at.”
Name of
Variant
Matsue
Activity in RBC
sex
(Kofnamsl)
F
F,M
M
F
M
M
75
5 inM
10
42
20
5
10
15
10
21
M
Tokyo
M
M
MGnchen
Creteil
M
M
M
M
SanFrancisco
M
3
17
8.2
12
Ebcbophastii
Mobility
ND
ND
Faster
ND
ND
Slower
ND
Slower
Normal
Slower
Slower
Slower
NO
Normal
Hen
Hmlylii
SCebili
Anemia
ND
ND
Low
ND
Normal
Low
ND
Low
ND
Low
Low
LOW
Normal
Normal
+
+
+
+
+
+
+
+
+
-
+
Neurologic
Abnomlities
Muacb
Disease
+
+
-
-
+
+
+
2
-
+
-
In addition to the 14 deficient variants listed above, several electrophoretic variants with normal activity were reported.
Abbreviations: F, female; M, male; ND, not described.
’The positionof amino acid substitution is counted from the NH,-terminal Ser.
-
h i m , AcM
Subniiution*
-
Arg+PrOat205
-
Leu+PrOat88
+
+
+
-
Val-Metat265
Asp-Asnot267
From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
1351
PHOSPHOGLYCERATE KINASE VARIANT (PGK-MATSUE)
PGK-Matsue is associated with a very severe enzyme
deficiency (about 5% of the normal level) in RBCs as well
as in nucleated ~ells.8.~
The patient suffered from chronic
hemolytic anemia and mental disorders, and died at age 9
from complications of pneumonia. The content of mRNA
in the patient's fibroblasts, estimated by the conventional
Northern blot hybridization and by the more accurate
quantitative liquid hybridization, was comparable with that
of normal fibroblasts." The specific enzyme activity of
PGK-Matsue was estimated to be about 35% to 40% of that
of normal PGK from the quantitative immunoneutralization test? Because the PGK activity in the patient's RBCs is
only 5% of that of normal cells, the molecular concentration of PGK-Matsue in the variant cells should be about
10% to 15% of that of normal cells. PGK-Matsue exhibited
higher Km values for all substrates, particularly for ATP
and 1,3-diphosphogly~erates.~
In the present study, a single T/A + C/G base transition
and a consequent amino acid substitution Leu -+ Pro at
position 88 from the NH,-terminal were found in PGKMatsue. The substitution position is in a random coil
between a-helices I1 (residues 77 through 87) and a
p-strand C (residues 91 through 94) of PGK
Because the pyrrolidine ring of the Pro residue causes a
substantial change in backbone torsional angle in a peptide
chain,'.2a structural instability and functional retardation
are expected to be induced in PGK-Matsue by the mutation. Indeed, all human hemoglobin and other protein
variants with the Leu + Pro substitution are
The major cause of a diminished concentration (10% to
15% of the normal level) of PGK-Matsue in RBCs and
other tissues is most likely a more rapid denaturation and
degradation of the variant enzyme originating from the
Leu + Pro substitution.
REFERENCES
1. Chen SH, Malcolm LA, Yoshida A, Giblett E Phosphoglycerate kinase: An X-linked polymorphism in man. Am J Hum Genet
23:87,1971
2. Willard HF, Goss SJ, Holmes MT, Munrose D L Regional
localization of the phosphoglycerate kinase gene and pseudogene
on the human X chromosome and assignment of a related DNA
sequence on chromosome 19. Hum Genet 71:138,1985
3. Huang I-Y, Welch CD, Yoshida A Complete amino acid
sequence of human phosphoglycerate kinase: Cyanogen bromide
peptides and complete amino acid sequence. J Biol Chem 255:
6412,1980
4. Michelson AM, Markham AF, Orkin SH: Isolation and DNA
sequence of a full-length cDNA clone for human X chromosomeencoded phosphoglycerate kinase. Proc Natl Acad Sci USA 80:472,
1983
5. Michelson AM, Blake CC, Evans ST, Orkin SH: Structure of
the human phosphoglycerate kinase gene and the intron-mediated
evolution and dispersal of the nucleotide-binding domain. Proc
Natl Acad Sci USA 82:6965,1985
6. Valentine WN, Hsieh HS, Paglia DE, Anderson HM, Baughan
MA, Jaffe ER, Garson OM: Hereditary hemolytic anemia associated with phosphoglycerate kinase deficiency in erythrocytes and
leukocytes: A probable X-chromosome-linked syndrome. N Engl J
Med 280528,1969
7. Rosa R, George C, Fardeau M, Calvin MC, Rapin M, Rosa J:
A new case of phosphoglycerate kinase deficiency: PGK Creteil
associated with rhabdomyolysis and lacking hemolytic anemia.
Blood 6084,1982
8. Miwa S, Nakashima K, Oda S, Ogawa H, Nagafuji H, Arima
M, Okuna T, Nakashima T: Phosphoglycerate kinase (PGK)
deficiency hereditary nonspherocytic hemolytic anemia: Report of
a case found in a Japanese family. Acta Hematol Jpn 35571, 1972
9. Yoshida A, Miwa S: Characterization of a phosphoglycerate
kinase variant associated with hemolytic anemia. Am J Hum Genet
26:378, 1974
10. Tani K, Takizawa T, Yoshida A Normal mRNA content in a
phosphoglycerate kinase variant with severe enzyme deficiency.
Am J Hum Genet 37931,1985
11. Maniatis T, Fritsch EF, Sambrook J: Molecular cloning: A
laboratory manual. Cold Spring Harbor, NY,Cold Spring Harbor
Laboratory, 1982
12. Saiki RK, Gelhnd DH, Stoffel S, Scharf SJ, Higuchi R, Horn
GT, Mullis KB, Erlich HA: Primer-directed enzymatic amplifica-
tion of DNA with a thermostable DNA polymerase. Science
239:487,1988
13. Singer-Sam J, Keith DH, Tani K, Simmer RL, Shively L,
Lindsay S, Yoshida A, R i g s AD: Sequence of the promoter region
of the gene for human X-linked 3 phosphoglycerate kinase. Gene
32:409,1984
14. Sanger F, Coulson AR, Barrett G, Smith AJH, Roe BA:
Cloning in single-stranded bacteriophage as an aid to rapid DNA
sequencing. J Mol Biol143:161,1980
15. Kraus AP,Langston MF, Lynch BL: Red cell phosphoglycerate kinase deficiency; a new case of non-spherocytic hemolytic
anemia. Biochem Biophys Res Commun 30:173,1968
16. Chen S-H, Giblett ER: Phosphoglycerate kinase: Additional
variants and their geographic distribution. Am J Hum Genet
24:229, 1972 (letter)
17. Fujii H, Krietsch WKG, Yoshida A A single amino acid
substitution (Asp Asn) in a phosphoglycerate kinase variant
(PGK Miinchen) associated with enzyme deficiency. J Biol Chem
255:6421,1980
18. Fujii H, Yoshida A Molecular abnormality of phosphoglycerate kinase Uppsala associated with chronic non-spherocytic
anemia. Proc Natl Acad Sci USA 775461,1980
19. Fujii H, Chen S-H, Akatsuka J, Yoshida A Use of cultured
lymphoblastoid cells for the study of abnormal enzymes: Molecular
abnormality of a phosphoglycerate kinase variant associated with
hemolytic anemia. Proc Natl Acad Sci USA 78:2587,1984
20. Yoshida A, Watanabe S: Human phosphoglycerate kinase,
I1 structure of a variant enzyme. J Biol Chem 247:446,1972
21. Yoshida A, Tani K Phosphoglycerate kinase abnormalities:
Functional, structural and genomic aspects. Biomed Biochim Acta
42:S263,1983
22. Banks RD, Blake CCF, Evans PR, Haser R, Rice DW,
Hardy GW, Menett M, Phillips AW: Sequence, structure and
activity of phosphoglycerate kinase: A possible hinge-bending
enzyme. Nature 279:773,1979
23. Kim PS, Baldwin R L Specific intermediates in the folding
reactions of small proteins and the mechanism of protein folding.
Ann Rev Biochem 51:459,1982
24. Pakula AA, Sauer R T Genetic analysis of protein stability
and function. Ann Rev Genet 23:289,1989
25. Burn HF, Forget BG, Ranney HM: Human hemoglobin
variants, in Burn HF, Forget BG, Ranney HM (eds): Human
Hemoglobins. Philadelphia, PA, Saunders, 1977, p 197
-
From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
1352
26. Takahashi H, Nukiwa T, Satoh K, Ogushi F, Brantly M, Fells
G, Stier L, Courtney M, Crystal RG: Characterization of the gene
and protein of the a,-antitrypsin “deficiency” allele M procida. J
Biol Chem 263:15528,1988
27. Hjelm M, Wadam B: Nonspherocytic hemolytic anemia with
phosphoglycerate kinase deficiency. XIIIth International Congress
of Hematology, Munich, Germany, 1970, p 121
28. Hjelm M, Wadam B, Yoshida A: A phosphoglycerate kinase
variant, PGK Uppsala, associated with hemolytic anemia. J Lab
Clin Med 96:1015,1980
29. Arese P, Bosia A, Gallo E, Mazza U, Pescarmona GP: Red
cell glycolysis in a case of 3-phosphoglycerate kinase deficiency.
Eur J Clin Invest 3:86,1973
30. Cartier P, Habibi B, Leroux JP, Marchand JC: Anemie
hemolytique congenilale associte a un deficit en phosphoglyckratekinase dans les globules rouges, les polynucleaires et les lymphocytes. Nouv Rev Fr Hematol11:565,1971
31. Konrad PN, McCarthy DJ, Mauer AM, Valentine WN,
Paglia DE: Erythrocyte and leukocyte phosphoglycerate kinase
deficiency with neurologic disease. J Pediatr 82:456, 1973
32. Akatsuka J, Saito F, Okabe N, Maekawa K, Kitani N,
MAEDA AND YOSHIDA
Nishina T, Hashimoto F Study of hereditary phosphoglycerate
kinase deficiency. Jpn J Clin Hematol 14:1189,1973
33. Boivin P, Hakim J, Mandereau J, Galand C, Degos F,
Shaison G: Dkficit en 3 phosphoglycerate kinase Crythrocytaire et
leucocytaire: Etude des propietes de I’enzyme, de la fonction
phagocytaire de polynucleaires et revue de la littkrature. Nouv Rev
Fr Hematol 14:495, 1974
34. Krietsch WK, Krietsch H, Kaiser W, Dunnwald M, Kuntz
GWK, Duhm J, Biicher T: Hereditary deficiency of phosphoglycerate kinase: A new variant in erythrocytes and leukocytes, not
associated with hemolytic anemia. Eur J Clin Invest 7:427, 1977
35. DiMauro S, Dalakas M, Miranda AF: Phosphoglycerate
kinase deficiency: Another cause of recurrent myoglobinuria. Ann
Neurol 13:11,1983
36. Sugie H, Sugie Y, Ichimura M, Tsurui S, Itoh M, Shimizu K,
Nishida H, Igarashi Y, Yonekawa 0, Kanno T: Phosphoglycerate
kinase deficiency with recurrent myoglobinuria. No To Hattatsu
18:36,1986
37. Guis MS, Karadsheh N, Mentzer WC: Phosphoglycerate
kinase San Francisco: A new variant associated with hemolytic
anemia but not with neuromuscular manifestations. Am J Hematol
25:175, 1987
From www.bloodjournal.org by guest on December 22, 2014. For personal use only.
1991 77: 1348-1352
Molecular defect of a phosphoglycerate kinase variant (PGK-Matsue)
associated with hemolytic anemia: Leu----Pro substitution caused by
T/A- ---C/G transition in exon 3
M Maeda and A Yoshida
Updated information and services can be found at:
http://www.bloodjournal.org/content/77/6/1348.full.html
Articles on similar topics can be found in the following Blood collections
Information about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests
Information about ordering reprints may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprints
Information about subscriptions and ASH membership may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American
Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.
Copyright 2011 by The American Society of Hematology; all rights reserved.