A MISSENSE MUTATION P136L IN THE ARYLSULFATASE-A GENE CAUSES INSTABILITY AND LOSS OF ACTIVITY OF THE MUTANT ENZYME

Metachromatic leukodystrophy is a lysosomal storage disease caused by deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of an Ashkenazi Jewish patient suffering from the severe late infanti le form of the disease revealed a point mutation in exon 2 causing pro line 136 to be substituted by leucine. The patient was homozygous for this mutation. Studies on Ltk(-) cells stably expressing the mutant en zyme show that the mutation causes complete loss of enzyme activity an d rapid degradation in an early biosynthetic compartment.