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. 1979 Apr;76(4):1957–1961. doi: 10.1073/pnas.76.4.1957

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

Chester DeLuca *, Judith A Brown †, Thomas B Shows ‡,§
PMCID: PMC383512  PMID: 36611

Abstract

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.

Keywords: somatic cell hybrids, human chromosomes 5 and 22, metachromatic leukodystrophy, Maroteaux-Lamy syndrome, multiple sulfatase deficiency

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Selected References

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  1. AUSTIN J. H., BALASUBRAMANIAN A. S., PATTABIRAMAN T. N., SARASWATHI S., BASU D. K., BACHHAWAT B. K. A CONTROLLED STUDY OF ENZYMIC ACTIVITIES IN THREE HUMAN DISORDERS OF GLYCOLIPID METABOLISM. J Neurochem. 1963 Dec;10:805–816. doi: 10.1111/j.1471-4159.1963.tb11905.x. [DOI] [PubMed] [Google Scholar]
  2. BAUM H., DODGSON K. S., SPENCER B. The assay of arylsulphatases A and B in human urine. Clin Chim Acta. 1959 May;4(3):453–455. doi: 10.1016/0009-8981(59)90119-6. [DOI] [PubMed] [Google Scholar]
  3. Bruns G. A., Mintz B. J., Leary A. C., Regina V. M., Gerald P. S. Expression of human arylsulfatase-A in man-hamster somatic cell hybrids. Cytogenet Cell Genet. 1978;22(1-6):182–185. doi: 10.1159/000130931. [DOI] [PubMed] [Google Scholar]
  4. Champion M. J., Shows T. B. Correction of human mucolipidosis II enzyme abnormalities in somatic cell hybrids. Nature. 1977 Nov 3;270(5632):64–66. doi: 10.1038/270064a0. [DOI] [PubMed] [Google Scholar]
  5. Champion M. J., Shows T. B. Electrophoretic abnormalities of lysosomal enzymes in mucolipidosis fibroblast lines. Am J Hum Genet. 1977 Mar;29(2):149–163. [PMC free article] [PubMed] [Google Scholar]
  6. Chan T. S., Reardon M. P., Greenstein R. M. Somatic cell hybrid assignment of a structural gene for human beta-glucuronidase to chromosome 7 by use of an X/7 translocation. Cytogenet Cell Genet. 1976;17(5):291–295. doi: 10.1159/000130725. [DOI] [PubMed] [Google Scholar]
  7. Eto Y., Wiesmann U. N., Carson J. H., Herschkowitz N. N. Multiple sulfatase deficiencies in cultured skin fibroblasts. Occurrence in patients with a variant form of metachromatic leukodystrophy. Arch Neurol. 1974 Feb;30(2):153–156. doi: 10.1001/archneur.1974.00490320041005. [DOI] [PubMed] [Google Scholar]
  8. Fluharty A. L., Stevens R. L., Davis L. L., Shapiro L. J., Kihara H. Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts. Am J Hum Genet. 1978 May;30(3):249–255. [PMC free article] [PubMed] [Google Scholar]
  9. Gilbert F., Kucherlapati R., Creagan R. P., Murnane M. J., Darlington G. J., Ruddle F. H. Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. Proc Natl Acad Sci U S A. 1975 Jan;72(1):263–267. doi: 10.1073/pnas.72.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goldstone A., Konecny P., Koenig H. Lysosomal hydrolases: Conversion of acidic to basic forms by neuraminidase. FEBS Lett. 1971 Feb 12;13(1):68–72. doi: 10.1016/0014-5793(71)80667-1. [DOI] [PubMed] [Google Scholar]
  11. Hellkuhl B., Grzeschik K. H. Assignment of a gene for arylsulfatase B to human chromosome 5 using human-mouse somatic cell hybrids. Cytogenet Cell Genet. 1978;22(1-6):203–206. doi: 10.1159/000130936. [DOI] [PubMed] [Google Scholar]
  12. Hook G. E., Dodgson K. S., Rose F. A., Worwood M. Relative distribution of arylsulphatases A and B in rat liver parenchymal and other cells. Biochem J. 1973 May;134(1):191–195. doi: 10.1042/bj1340191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lalley P. A., Brown J. A., Eddy R. L., Haley L. L., Byers M. G., Goggin A. P., Shows T. B. Human beta-glucuronidase: assignment of the structural gene to chromosome 7 using somatic cell hybrids. Biochem Genet. 1977 Apr;15(3-4):367–382. doi: 10.1007/BF00484467. [DOI] [PubMed] [Google Scholar]
  14. Lalley P. A., Rattazzi M. C., Shows T. B. Human beta-D-N-acetylhexosaminidases A and B: expression and linkage relationships in somatic cell hybrids. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1569–1573. doi: 10.1073/pnas.71.4.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lalley P. A., Shows T. B. Expression of human hexosaminidase-A phenotype depends on genes assigned to chromosomes 5 and 15. Cytogenet Cell Genet. 1976;16(1-5):192–196. doi: 10.1159/000130588. [DOI] [PubMed] [Google Scholar]
  16. MEHL E., JATZKEWITZ H. EVIDENCE FOR THE GENETIC BLOCK IN METACHROMATIC LEUCODYSTROPHY (ML). Biochem Biophys Res Commun. 1965 May 3;19:407–411. doi: 10.1016/0006-291x(65)90137-3. [DOI] [PubMed] [Google Scholar]
  17. Matalon R., Arbogast B., Dorfman A. Deficiency of chondroitin sulfate N-acetylgalactosamine 4-sulfate sulfatase in Maroteaux-Lamy syndrome. Biochem Biophys Res Commun. 1974 Dec 23;61(4):1450–1457. doi: 10.1016/s0006-291x(74)80446-8. [DOI] [PubMed] [Google Scholar]
  18. Naylor S. L., Klebe R. J., Shows T. B. Argininosuccinic aciduria: assignment of the argininosuccinate lyase gene to the pter to q22 region of human chromosome 7 by bioautography. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6159–6162. doi: 10.1073/pnas.75.12.6159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neuwelt E., Stumpf D., Austin J., Kohler P. A monospecific antibody to human sulfatase A. Preparation, characterization and significance. Biochim Biophys Acta. 1971 Apr 27;236(1):333–346. doi: 10.1016/0005-2795(71)90182-6. [DOI] [PubMed] [Google Scholar]
  20. O'Brien J. F., Cantz M., Spranger J. Maroteaux-Lamy disease (mucopolysaccharidosis VI), subtype A: deficiency of a N-acetylgalactosamine-4-sulfatase. Biochem Biophys Res Commun. 1974 Oct 8;60(3):1170–1177. doi: 10.1016/0006-291x(74)90435-5. [DOI] [PubMed] [Google Scholar]
  21. Owerbach D., Doyle D., Shows T. B. Genetics of the large, external, transformation-sensitive (LETS) protein: assignment of a gene coding for expression of LETS to human chromosome 8. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5640–5644. doi: 10.1073/pnas.75.11.5640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rattazzi M. C., Marks J. S., Davidson R. G. Electrophoresis of arylsulfatase from normal individuals and patients with metachromatic leukodystrophy. Am J Hum Genet. 1973 May;25(3):310–316. [PMC free article] [PubMed] [Google Scholar]
  23. Roy A. B. Sulphatases, lysosomes and disease. Aust J Exp Biol Med Sci. 1976 Apr;54(2):111–135. doi: 10.1038/icb.1976.13. [DOI] [PubMed] [Google Scholar]
  24. Shapira E., DeGregorio R. R., Matalon R., Nadler H. L. Reduced arylsulfatase B activity of the mutant enzyme protein in Maroteaux-Lamy syndrome. Biochem Biophys Res Commun. 1975 Jan 20;62(2):448–455. doi: 10.1016/s0006-291x(75)80159-8. [DOI] [PubMed] [Google Scholar]
  25. Shows T. B., Brown J. A. Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2125–2129. doi: 10.1073/pnas.72.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shows T. B. Genetics of human-mouse somatic cell hybrids: linkage of human genes for lactate dehydrogenase-A and esterase-A 4 . Proc Natl Acad Sci U S A. 1972 Feb;69(2):348–352. doi: 10.1073/pnas.69.2.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shows T. B., Scrafford-Wolff L. R., Brown J. A., Meisler M. H. GM1-gangliosidosis: chromosome 3 assignment of the beta-galactosidase-A gene (beta GALA). Somatic Cell Genet. 1979 Mar;5(2):147–158. doi: 10.1007/BF01539157. [DOI] [PubMed] [Google Scholar]
  28. Sparkes R. S., Mohandas T., Sparkes M. C., Shulkin J. D. Aconitase (E.C. 4.2.1.3) mitochondrial locus mapped to human chromosome 22: studies with Chinese hamster--human somatic cell hybrids. Biochem Genet. 1978 Aug;16(7-8):751–756. doi: 10.1007/BF00484732. [DOI] [PubMed] [Google Scholar]
  29. Spranger J. W., Koch F., McKusick V. A., Natzschka J., Wiedemann H. R., Zellweger H. Mucopolysaccharidosis VI (Maroteaux-Lamy's disease). Helv Paediatr Acta. 1970 Oct;25(4):337–362. [PubMed] [Google Scholar]
  30. Stumpf D. A., Austin J. H., Crocker A. C., LaFrance M. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). I. Sulfatase B deficiency in tissues. Am J Dis Child. 1973 Dec;126(6):747–755. doi: 10.1001/archpedi.1973.02110190597003. [DOI] [PubMed] [Google Scholar]
  31. Swallow D. M., Harris H. A new variant of the placental acid phosphatases: its implications regarding their subunit structures and genetical determination. Ann Hum Genet. 1972 Nov;36(2):141–152. doi: 10.1111/j.1469-1809.1972.tb00765.x. [DOI] [PubMed] [Google Scholar]

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