Adcnylatc kinaso (ATP-AMP phosphotransferase) is an ubiquitous cnzvme present in three isofornis (AK 1-3). The crvthocvlic isoenzyme (AK I) is encoded by a 12 kb long gene, splittcd in 7 e\ons. Seven cases of red cell AK deficiency have been so far reported, hi all cases but one the enzyme deficiency was associated with congenital non-spherocvtic hcmoKtic anemia. Only one mutation (CGG-TGG Arg 128-Trp) has been reported in a patient \\ith adenylatc kinasc deficiency. The aim of this study is to describe the hematological. biochemical and molecular characteristics of a new defective AK variant associated with chronic hemolxtic anemia. The propositus vvas a 4 vrs old boy of Northern Italian origin with a history of chronic hemolvtic anemia and occasional need for blood transfusions during infectious episodes. At the time of the study. Hb was K).K g/dL. retictilocvtes 278\109/L. unconjugated bilimbin 13 tng/dL The study of the most important red cell enzymes did not reveal am abnormality except for AK activity that was absent. Strictly similar hematological and metabolic findings were detected in the 5 yrs old sister. The parents were not consanguineous and displayed intermediate AK activity (55 and 70% of normal, respective!) ) The sequence of complete erythrocvtc AKI cDNA showed the presence of a nonsense homozvgous mutation at codon 107 (CGA-TGA. Arg-Stop) in the proband and the sister. The mutation results in a truncated protein of 107 amino acids in comparison w ith the 194 of the normal one. It determines the lack of amino acids involved in the functional properties of the protein justify ing the absence of enzyme activity in the patient and in the sister. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected: this deletion is likely not to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza. from the origin of the patient.
|Number of pages||1|
|Publication status||Published - 1997|
ASJC Scopus subject areas
- Cancer Research
- Cell Biology