Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B

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Genetics of human lysosomal arylsulfatases A and B (aryl-sulfate sulfohydrolase, EC 3.1.6.1), associated with childhood disease, has been studied with human-rodent somatic cell hybrids. Deficiency of arylsulfatase A (ARSA) in humans results in a progressive neurodegenerative disease, metachromatic leukodystrophy. Deficiency of arylsulfatase B (ARSB) is associated with skeletal and growth malformations, termed the Maroteaux-Lamy syndrome. Simultaneous deficiency of both enzymes is associated with the multiple sulfatase deficiency disease, suggesting a common relationship for ARSA and ARSB. The genetic and structural relationships of human ARSA and ARSB have been determined by the use of human-Chinese hamster somatic cell hybrids. Independent enzyme segregation in cell hybrids demonstrated different chromosome assignments for the structural genes, ARSA and ARSB, coding for the two lysosomal enzymes. ARSA activity showed concordant segregation with mitochondrial aconitase encoded by a gene assigned to chromosome 22. ARSB segregated with β-hexosaminidase B encoded by a gene assigned to chromosome 5. These assignments were confirmed by chromosome analyses. The subunit structures of ARSA and ARSB were determined by their electrophoretic patterns in cell hybrids; a dimeric structure was demonstrated for ARSA and a monomeric structure for ARSB. Although the multiple sulfatase deficiency disorder suggests a shared relationship between ARSA and ARSB, independent segregation of these enzymes in cell hybrids did not support a common polypeptide subunit or structural gene assignment. The evidence demonstrates the assignment of ARSA to chromosome 22 and ARSB to chromosome 5. A third gene that affects ARSA and ARSB activity is suggested by the multiple sulfatase deficiency disorder.

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