A novel in-frame deletion mutation in a case of lactate dehydrogenase (LD)H subunit deficiency showing an atypical LD isoenzyme pattern in serum anderythrocytes

Objective: We report a case showing an atypical lactate dehydrogenase (LD) isoenzyme pattern involving deficiency only of LD-1 and LD-2 in serum and e rythrocytes. LD activity in serum from this patient was extremely low, simi lar to complete LD-H deficiency, and also that in erythrocytes was low. Design: The DNA fragment containing exon 1 through 7 of the LD-H gene were amplified by PCR and directly sequenced. Total RNA was prepared from venous blood and the proportion of LD-H cDNA to total LD cDNA was semiquantified. Results: Genetic analysis by DNA sequencing detected a three base deletion (AAT) at codon 220 of exon 5, which caused a deletion of one asparagine. Th e present case did not show reduced LD-H expression at the mRNA level in wh ole blood. Residue 220 is involved in turning beta-J to alpha(1)-G and is n ot buried in the interior of the protein. The novel homozygous in-frame del etion mutation at codon 220 may cause a three-dimensional change of the sub unit-binding domain. Copyright (C) 1999 The Canadian Society of Clinical Ch emists.