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A case of PDH‐E1α mosaicism in a male patient with severe metabolic lactic acidosis
Author(s) -
Seyda A.,
Chun K.,
Packman S.,
Robinson B. H.
Publication year - 2001
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1012463726810
Subject(s) - lactic acidosis , metabolic acidosis , metabolic disease , medicine , acidosis , endocrinology , biology
We have characterized a novel mutation in a male patient that affects the coding sequence of PDH‐E 1 α gene and changes arginine‐141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fibroblasts, liver and muscle), a scenario that would indicate a case of E 1 α mosaicism in a male patient. When the mutant E 1 α protein was expressed in human skin fibroblasts with zero endogenous pyruvate dehydrogenase complex activity and E 1 α protein expression, no significant restoration of activity was recorded, in contrast to the wild‐type cDNA, even though both wild‐type and mutant protein levels were comparable. We concluded that the R141L mutation is a severe one and that it must have occurred in one of the E 1 α alleles during early embryogenesis.