ARYLSULFATASE A PSEUDODEFICIENCY-ASSOCIATED MUTATIONS - POPULATION STUDIES AND IDENTIFICATION OF A NOVEL HAPLOTYPE

Pseudodeficiency of arylsulfatase A is characterized by reduction of a rylsulfatase A activity without neurodegeneration, making it an import ant complication when diagnosing metachromatic leukodystrophy, Two DNA substitutions are associated with arylsulfatase A pseudodeficiency. O ne, 1788A-->G, results in the loss of an N-glycosylated asparagine in the protein, and the second, 2723A-->G, removes the polyadenylation si gnal site of the mRNA, Previously, the polyadenylation signal site var iant was observed only in the presence of the N-glycosylation site var iant, although the latter has been reported to occur in the absence of the polyadenylation signal site variant, We investigated the frequenc ies of these alleles and their linkage disequilibrium in a number of p opulations and in psychiatric patients, While the N-glycosylation site variant had a high frequency in the Bantu-speaking people from Southe rn Africa (0.44), the San of Southern Africa (0.22), African Americans (0.37), and Cheyenne Indians (0.375), the polyadenylation signal site variant was absent in these groups, The mutated polyadenylation signa l site was found only in the Caucasian groups surveyed. Two Caucasian sibs were identified with the pseudodeficiency polyadenylation signal site variant in the absence of the N-glycosylation site variant, indic ating that linkage disequilibrium between the two polymorphisms is not perfect. (C) 1996 Wiley-Liss, Inc.