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Article: Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong

TitleHereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong
Authors
Issue Date1994
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 1994, v. 84 n. 10, p. 3505-3509 How to Cite?
AbstractWe identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT → GTT, resulting in a single amino acid substitution from 468Ala → Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT → ACT, resulting in a single amino acid substitution from 314Ile → Thr. The R-PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme.
Persistent Identifierhttp://hdl.handle.net/10722/148009
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKanno, Hen_US
dc.contributor.authorWei, DCen_US
dc.contributor.authorChan, LCen_US
dc.contributor.authorMizoguchi, Hen_US
dc.contributor.authorAndo, Men_US
dc.contributor.authorNakahata, Ten_US
dc.contributor.authorNarisawa, Ken_US
dc.contributor.authorFujii, Hen_US
dc.contributor.authorMiwa, Sen_US
dc.date.accessioned2012-05-29T06:10:21Z-
dc.date.available2012-05-29T06:10:21Z-
dc.date.issued1994en_US
dc.identifier.citationBlood, 1994, v. 84 n. 10, p. 3505-3509en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttp://hdl.handle.net/10722/148009-
dc.description.abstractWe identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT → GTT, resulting in a single amino acid substitution from 468Ala → Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT → ACT, resulting in a single amino acid substitution from 314Ile → Thr. The R-PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme.en_US
dc.languageengen_US
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_US
dc.relation.ispartofBlooden_US
dc.subject.meshAdulten_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnemia, Hemolytic - Blood - Enzymology - Geneticsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshDna Primersen_US
dc.subject.meshErythrocytes - Enzymologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHong Kongen_US
dc.subject.meshHumansen_US
dc.subject.meshJapanen_US
dc.subject.meshMaleen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPedigreeen_US
dc.subject.meshPoint Mutationen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPyruvate Kinase - Blood - Geneticsen_US
dc.titleHereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kongen_US
dc.typeArticleen_US
dc.identifier.emailChan, LC:chanlc@hkucc.hku.hken_US
dc.identifier.authorityChan, LC=rp00373en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7949104-
dc.identifier.scopuseid_2-s2.0-0028089699en_US
dc.identifier.volume84en_US
dc.identifier.issue10en_US
dc.identifier.spage3505en_US
dc.identifier.epage3509en_US
dc.identifier.isiWOS:A1994PR22100030-
dc.publisher.placeUnited Statesen_US

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