Severe erythrocyte adenylate kinase deficiency due to homozygous A-->G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia.
A child of Italian origin with a congenital haemolytic anaemia had spectrophotometrically undetectable erythrocyte adenylate kinase (AK) activity. Her parents and brother had approximately 50% normal AK activity, and AK electrophoresis of red blood cell (RBC) crude extract on cellulose acetate strips showed the presence of the normal allele AK1-1. No AK band was detected in the AK electrophoresis of the proband, in whom the erythrocyte 2,3-diphosphoglycerate (2,3DPG) and glutathione (GSH) concentrations were normal whereas adenosine triphosphate (ATP) concentration, pyruvate kinase (PK) and glucose-6P-dehydrogenase (G6PD) activities were increased, reflecting the high reticulocyte count (6.9%). No other evident enzymatic defect was detected by standard procedures. Analysis of AK gene exons, based on polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP), clearly showed an abnormality in the fragment containing exon 6. The subsequent sequence analysis of this abnormal fragment revealed homozygous and heterozygous A-->G substitutions in the proband and in the parents and brother respectively at codon 164, corresponding to a tyrosine-->cysteine substitution in the AK protein.
Qualtieri
A
A
Centro Studi della Microcitemia, Cosenza, Italy.
Pedace
V
V
Bisconte
M G
MG
Bria
M
M
Gulino
B
B
Andreoli
V
V
Brancati
C
C
D000263:Adenylate Kinase / Q000172:deficiency* / Q000235:genetics; D019943:Amino Acid Substitution; D000743:Anemia, Hemolytic / Q000201:enzymology / Q000235:genetics*; D002648:Child; D004588:Electrophoresis, Cellulose Acetate; D004912:Erythrocytes / Q000201:enzymology*; D005091:Exons; D005260:Female; D005784:Gene Amplification; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000263:Adenylate Kinase