Cultured skin fibroblasts from patients with different clinical types of Niemann-Pick disease were hybridized and sphingomyelinase activities were measured in the heterokaryon cell population. Both the natural substrate (3H-choline) sphingomyelin and the chromogenic analogue hexadecanoylamino-4-nitrophenylphosphorylcholine were used in the complementation analysis. In fusions between cells from type C Niemann-Pick disease with those from type A or B a clear restoration of sphingomyelinase activity occurred, whereas no complementation was found in other fusion combinations. The results indicate that at least two different genes are involved in the mutations leading to the different Niemann-Pick variants.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Besley, G. T. N.: Sphingomyelinase defect in Niemann-Pick disease, type C, fibroblasts. FEBS Lett. 80, 71–74 (1977)
Brady, R. O.: Sphingomyelin lipidosis: Niemann-Pick disease. In: The metabolic basis of inherited disease (J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, eds.), pp. 718–730. New York: McGraw-Hill 1978
Callahan, J. W., Khalil, M., Gerrie, J.: Isoenzymes of sphingomyelinase and the genetic defect in Niemann-Pick disease, type C. Biochem. Biophys. Res. Commun. 58, 384–390 (1974)
Callahan, J. W., Khalil, M., Philippart, M.: Sphingomyelinases in human tissues. Absence of a specific enzyme from liver and brain of Niemann-Pick disease, type C. Pediatr. Res. 9, 908–913 (1975)
Dewhurst, N., Besley, G. T. N., Finlayson, N. D. O., Parker, A. L.: Sea-blue histiocytosis in a patient with chronic nonneuropathic Niemann-Pick disease. J. Clin. Pathol., in press (1980)
Gal, A. E., Brady, R. O., Hibbert, S. R., Pentchev, P. G.: A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease. New Engl. J. Med. 293, 632–636 (1975)
Galjaard, H., Hoogeveen, A., de Wit-Verbeek, H. A., Reuser, A. J. J., Keijzer, W., Westerveld, A., Bootsma, D.: Tay-Sachs and Sandhoff disease: Intergenic complementation after somatic cell hybridization. Exp. Cell Res. 87, 444–448 (1974)
Galjaard, H., Hoogeveen, A., Keijzer, W., de Wit-Verbeek, H. A., Reuser, A. J. J., Ho, M. W., Robinson, D.: Genetic heterogeneity in G-gangliosidosis. Nature 257, 60–62 (1975)
Gravel, R. A., Mahoney, M. J., Ruddle, F. H., Rosenberg, L. E.: Genetic complementation in heterokaryons of human fibroblasts defective in cobalamin metabolism. Proc. Natl. Acad. Sci. 72, 3181–3185 (1975)
Karpati, G., Carpenter, S., Wolfe, L. S., Andermann, F.: Juvenile dystonic lipidosis: An unusual form of neurovisceral storage disease. Neurology 27, 32–42 (1977)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)
Mraz, W., Fischer, G., Jatzkewitz, H.: Low molecular weight proteins in secondary lysosomes as activators of different sphingolipid hydrolases. FEBS Lett 67, 104–109 (1976)
Pentchev, P. G., Brady, R. O., Gal, A. E., Hibbert, S. R.: The isolation and characterisation of sphingomyelinase from human placenta. Biochim. Biophys. Acta 488, 312–321 (1977)
Schneider, E. L., Penchev, P. G., Hibbert, S. R., Sawitzky, A., Brady, R. O.: A new form of Niemann-Pick disease characterised by temperature-labile sphingomyelinase. J. Med. Genet. 15, 370–374 (1978)
Singh, S., Willers, I., Goedde, H. W.: Heterogeneity in maple syrup urine disease. Aspects of cofactor requirement and complementation in cultured fibroblasts. Clin. Genet. 11, 277–284 (1977)
de Weerd-Kastelein, E. A., Keijzer, W., Bootsma, D.: Genetic heterogeneity of xeroderma pigmentosum demonstrated by somatic hybridization. Nature 238, 80–83 (1972)
Wenger, D. A., Barth, G., Githens, J. H.: Nine cases of sphingomyelin lipidosis, a new variant in Spanish-American children. Am. J. Dis. Child. 131, 955–961 (1977)
Yamaguchi, S., Suzuki, K.: Purification and characterization of sphingomyelinase from human brain. J. Biol. Chem. 52, 3805–3813 (1977a)
Yamaguchi, S., Suzuki, K.: Sphingomyelinase isoenzymes of human tissues: A hypothesis on enzymatic differentiation of the neuropathic and non-neuropathic forms of Niemann-Pick disease. Biochem. Biophys. Res. Commun. 77, 999–1003 (1977b)
About this article
Cite this article
Besley, G.T.N., Hoogeboom, A.J.M., Hoogeveen, A. et al. Somatic cell hybridisation studies showing different gene mutations in Niemann-Pick variants. Hum Genet 54, 409–412 (1980). https://doi.org/10.1007/BF00291589
- Internal Medicine
- Cell Population
- Metabolic Disease
- Gene Mutation
- Somatic Cell