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Mercaptopyruvate sulfurtransferase (MPST) catalyzes the conversion of 3-mercaptopyruvate to pyruvate and persulfide, essential for cysteine degradation and cyanide detoxification. Deficiency in MPST activity underlies the rare autosomal recessive encephalopathy due to beta-mercaptolactate-cysteine disulfiduria (encephalopathy due to beta-mercaptolactate-cysteine disulfiduria).
In a cohort of 50 unrelated French individuals, a single nonsense mutation, Tyr85Stop, and two intronic polymorphisms (IVS1-110C>G, IVS2+39C>T) were identified; the truncating allele led to severely reduced erythrocyte MPST activity in vivo and loss of enzymatic function in heterologous expression and transient transfection assays (PMID:16545926).
Inheritance is autosomal recessive, with no additional affected relatives reported. Genetic evidence is limited to a single truncating variant without segregation data. Functional assays provide moderate evidence of loss of enzyme activity concordant with disease biochemistry.
Key take-home: Truncating MPST alleles abolish sulfurtransferase activity, supporting a recessive molecular basis for encephalopathy due to beta-mercaptolactate-cysteine disulfiduria and informing genetic testing strategies.
Gene–Disease AssociationLimitedSingle proband with truncating variant in MPST and no segregation Genetic EvidenceLimitedIdentification of a single nonsense allele (p.Tyr85Ter) in one individual, without familial segregation ([PMID:16545926]) Functional EvidenceModerateIn vivo enzyme deficiency and in vitro expression assays demonstrate loss of MPST activity ([PMID:16545926]) |