Evidence for a functional genetic polymorphism of the human mercaptopyruvate sulfurtransferase (MPST), a cyanide detoxification enzyme.
Mercaptopyruvate sulfurtransferase (MPST) plays a central role in both cysteine degradation and cyanide detoxification. Moreover, deficiency in MPST activity has been suggested to be responsible for a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). To date, no mutation of the human MPST gene has been reported. We developed a screening strategy to search for mutations in the MPST gene of 50 unrelated French individuals. Two intronic polymorphisms (IVS1-110C>G and IVS2+39C>T) and a nonsense mutation (Tyr(85)Stop) were identified and their functional consequences were assessed in vivo by measurement of erythrocyte MPST activity and/or in vitro using heterologous expression or transient transfection assay. The nonsense mutation likely leads to the synthesis of a severely truncated protein without enzymatic activity, as supported by our in vitro data. This work constitutes the first report of the existence of a functional genetic polymorphism affecting MPST and should be of great help to investigate certain disorders such as MCDU.
Billaut-Laden
Ingrid
I
Equipe d'accueil EA2679, Faculté de Médecine, Pôle Recherche, 1 place de Verdun, 59045 Lille Cedex, France.
Rat
Emmanuel
E
Allorge
Delphine
D
Crunelle-Thibaut
Aurélie
A
Cauffiez
Christelle
C
Chevalier
Dany
D
Lo-Guidice
Jean-Marc
JM
Broly
Franck
F
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D003486:Cyanides / Q000097:blood*; D017931:DNA Primers / Q000737:chemistry; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013466:Sulfurtransferases / Q000097:blood / Q000172:deficiency / Q000235:genetics*
D018389:Codon, Nonsense; D003486:Cyanides; D017931:DNA Primers; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase