A novel mutation found in a study of sprint exercise performance in AMP deaminase deficiency

Abstract

We here report a novel mutation found in subjects that lacked AMPD activity and were heterozygote for the C34T in the AMPD1 gene. AMP deaminase (AMPD) deficiency is an inherited disorder of skeletal muscle found in approximately 2% of Caucasian population. The deficiency is connected with an altered ATP catabolism and a loss of increase in plasma ammonia in response to high intensity exercise. In most cases the deficiency is due to a C34T transition in the AMPD1-gene. In a study with 139 healthy, physically active subjects of both genders, 12 AMPD-deficient subjects were studied. Although, 3 of the subjects were not homozygote for the C34T polymorphism. Sequencing and allele-specific PCR amplification assays were used to identify the mutation and a single nucleotide deletion in exon 5, 404delT was found. The frameshift mutation results in a premature termination of translation at codon 175. Three of the deficient subjects were compound heterozygote carrying the common C34T and the 404delT mutation. A 30-s Wingate test was used to assess muscle power, muscle endurance, and fatigability. The healthy AMPD-deficient subjects performed an approximately 10% lower mean power.