A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency.

Fumarase hydratase (FH) deficiency is a rare familial disorder of the tricarboxylic acid cycle which is characterized by severe neurological impairment in early childhood. Several autosomal recessive mutations in the fumarate hydratase gene have been identified as a cause of the lack of fumarase activity in affected individuals. We describe a novel mutation in nucleotide 1127A>C of the fumarase cDNA which changes glutamine 376 to proline in the vicinity of the catalytic site and explains the loss of FH function.