title: First missense mutations (R388W and R425H) of AMPD1 accompanied with myopathy found in a Japanese patient.
abstract: Skeletal muscle AMP deaminase (AMPD: E.C. 3.5.4.6) deficiency is one of the most common inherited defects in the Caucasians, but not in Asians. Although a diagnosis of AMPD1 deficiency is indeed based on the reduced enzymatic activity, its clinical significance is still rather controversial since most subjects are asymptomatic. Alternative splicing of exon 2 in individuals who have inherited this defect is thought to provide a mechanism for phenotypic rescue that may explain the variability of clinical symptoms as we reported earlier. In this report we present the first case with a detectable defect of the AMPD1 gene in a Japanese patient with myopathy. Two missense mutations (R388W and R425H) in exon 9 and exon 10 of the AMPD1 gene were found. Prokaryotic expression showed a comparable amount of the AMPD1 peptides and undetectable AMPD activity in the constructs with these mutations. From this study, we have concluded that this patient is a compound heterozygote for AMPD1 mutant allele. This study also demonstrates the first reported instance of detectable dysfunction of the AMPD1 gene product, suggesting that AMPD1 indeed has a key role in muscle metabolism and function.
authors: Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan. morisaki@ri.ncvc.go.jp
authors: H
authors: H
authors: Morisaki
authors: I
authors: I
authors: Higuchi
authors: M
authors: M
authors: Abe
authors: M
authors: M
authors: Osame
authors: T
authors: T
authors: Morisaki
mesh_terms: D000659:AMP Deaminase / Q000172:deficiency / Q000235:genetics*; D000328:Adult; D001120:Arginine / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D006639:Histidine / Q000235:genetics; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D014162:Transfection; D014364:Tryptophan / Q000235:genetics
chemical_list: D006639:Histidine; D014364:Tryptophan; D001120:Arginine; D000659:AMP Deaminase