Creatine kinase gene mutation in a patient with muscle creatine kinase deficiency

Background: We describe a 56-year-old woman admitted to the hospital with a diagnosis of acute myocardial infarction without an increase of serum crea tine kinase (CK) activity during her clinical course. She died on the 11th hospital day, and the diagnosis was confirmed by autopsy. The patient had h ad no previous muscular symptoms. Methods: Expression of the CK-muscle (CK-M) protein in cardiac tissue was e xamined by immunoblotting and immunochemical staining. CK-M mRNA expression was estimated by semiquantitative reverse transcription-PCR. Gene structur e of CK-M was determined by Southern blotting and direct sequencing of 2251 bp. Existence of a point mutation in the CK-M gene was examined by restric tion fragment length polymorphism analysis of PCR products (PCR-RFLP) in th e patient and in 108 controls. Results: CK-M protein in the myocardial tissue of the patient was substanti ally lower (103 +/- 7 ng/mg protein) than in control myocardial tissue (35 800 +/- 2860 ng/mg protein). Immunoreactive CK-M in the patient tissue samp le was 0.3% of the value for the control sample. CK-M mRNA was 53-fold less in the patient sample compared with the control. This very low expression of CK-M mRNA was considered to be the primary reason for CK-M deficiency. D irect sequencing revealed a point mutation at residue 54 in exon 2, which w as specific for the patient. No other abnormalities were found in the CK-M gene of the patient. Conclusions: This report identifies a molecular abnormality in human CK def iciency and discusses the physiologic relevance of CK-M. (C) 2001 American Association for Clinical Chemistry.