CHARACTERIZATION OF 2 ARYLSULFATASE-A MISSENSE MUTATIONS D335V AND T274M CAUSING LATE INFANTILE METACHROMATIC LEUKODYSTROPHY

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A, We describe a novel missense mutat ion in exon 6 causing the substitution of Asp335 by Val, In transient transfections no enzyme activity could be expressed from the arylsulfa tase A cDNA carrying this mutation. Examination of the effects of the mutation in cells stably overexpressing the mutant enzyme revealed, th at the mutant enzyme is catalytically inactive and degraded in an earl y biosynthetic compartment, We have also investigated the effects of a previously identified mutation (T274M), The specific catalytic activi ty of the Met274 substituted arylsulfatase is reduced to about 35% of the normal enzyme when measured with an artificial substrate, Most of this enzyme is also degraded in an early biosynthetic compartment. (C) 1996 Wiley-Liss, Inc.