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Severe erythrocyte adenylate kinase deficiency due to homozygous A → G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia
Author(s) -
Qualtieri A.,
Pedace V.,
Bisconte M. G.,
Bria M.,
Gulino B.,
Andreoli V.,
Brancati C.
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.4953299.x
Subject(s) - microbiology and biotechnology , adenylate kinase , biology , exon , isoelectric focusing , biochemistry , chemistry , gene , enzyme
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.