title: Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications.
abstract: At the locus for arylsulfatase A (ASA) at least four to five alleles exist: besides the normal ASA+ and at least two to three deficiency alleles (ASA-), a pseudodeficiency allele, ASAp, is known. On SDS-PAGE the ASAp enzyme migrates slightly faster than ASA+. Treatment of extracts from cells with ASA+/ASA+, ASAp/ASAp, or ASA+/ASAp genotypes with endoglycosidase F leads to the same deglycosylated subunit pattern. Presumably the degree of glycosylation is lower in ASAp than in ASA+. In a large-scale screening project we determined a gene frequency of 7.3% for ASAp. Thus, the ASA locus is polymorphic. In seven families, ASAp showed a codominant mode of inheritance with ASA+. Homozygosity for ASAp has no obvious clinical consequences. In subjects with the compound genotype ASA-/ASAp, the residual enzyme activity may fall below a critical threshold, so that the substrate can no longer be hydrolyzed sufficiently. Since these compounds are not so rare (estimated frequency 0.073%), this mechanism could be of importance in neuropsychiatric disorders with late onset.
authors.affiliation: Institut für Humangenetik der Universität, Bonn, Federal Republic of Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hohenschutz
authors.forename: P
authors.initials: P
authors.lastname: Eich
authors.forename: W
authors.initials: W
authors.lastname: Friedl
authors.forename: A
authors.initials: A
authors.lastname: Waheed
authors.forename: E
authors.initials: E
authors.lastname: Conzelmann
authors.forename: P
authors.initials: P
authors.lastname: Propping
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D002553:Cerebroside-Sulfatase / Q000172:deficiency / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics; D008970:Molecular Weight; D010375:Pedigree; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000201:enzymology / Q000235:genetics
chemical_list: D002553:Cerebroside-Sulfatase