RGD Reference Report - Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong. - Rat Genome Database

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

Authors: Kanno, H  Wei, DC  Chan, LC  Mizoguchi, H  Ando, M  Nakahata, T  Narisawa, K  Fujii, H  Miwa, S 
Citation: Kanno H, etal., Blood. 1994 Nov 15;84(10):3505-9.
RGD ID: 11535979
Pubmed: PMID:7949104   (View Abstract at PubMed)

We 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 468la-->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 314lle-->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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congenital nonspherocytic hemolytic anemia  IAGP 11535979DNA:missense mutations:cds:p.A468V and p.I314T (human)RGD 
congenital nonspherocytic hemolytic anemia  ISOPKLR (Homo sapiens)11535979; 11535979DNA:missense mutations:cds:p.A468V and p.I314T (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reduced red cell pyruvate kinase level  IAGP 11535979DNA:missense mutations:cds:p.A468V and p.I314T RGD 
Objects Annotated

Genes (Rattus norvegicus)
Pklr  (pyruvate kinase L/R)

Genes (Mus musculus)
Pklr  (pyruvate kinase liver and red blood cell)

Genes (Homo sapiens)
PKLR  (pyruvate kinase L/R)


Additional Information