Molecular heterogeneity of Krabbe disease
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Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and peripheral nervous system due to an enzymatic defect of galactocerebrosidase (GALC). Following its cloning, many mutations in the galactocerebrosidase gene have been reported, but the correlation between phenotype and genotype was not clear in many cases. In this study we further investigated the molecular defects in another 10 patients (6 Japanese and 4 non-Japanese), using cultured skin fibroblasts, and found 10 mutations, of which 8 were novel, including a nonsense mutation (W647X) and 7 missense mutations (G43R, S52F, T262I, Y319C, W410G, R515H, T652R) in the coding region. Some phenotype-specific mutations were found but the other mutations were private. Mutations reported so far have been distributed over the whole GALC gene and it is difficult to speculate on functional domains of the GALC protein and phenotypically specific regions.
- Austin JH (1968) Globoid (Krabbe) leukodystrophy. In Minkler J (ed.), Pathology of the Nervous System. McGraw-Hill, New York, 843-853.
- Bernardini GL, Herrera DG, Carson D, et al (1997) Adult-onset KrabbeÏs disease in siblings with novel mutations in galactocerebrosidase gene. Ann Neurol 41: 111-114.
- Chen Y Q, Wenger, DA (1993) Galactocerebrosidase from human urine: purification and partial characterization. Biochim Biophys Acta 1170: 53-61.
- Chen YQ, Rafi MA, de Gala G, Wenger DA (1993) Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy. Hum Mol Genet 2: 1841-1845.
- de Gasperi R, Gama Sosa MA, Sartorato EL, et al (1996) Molecular heterogeneity of lateonset forms of globoid-cell leukodystrophy. Am J Hum Genet 59: 1233-1242.
- Furuya H, Kukita Y, Nagano S, et al (1997) Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients. Hum Genet 100: 450-456.
- Kolodny EH, Raghavans S, Krivit W (1991) Late-onset Krabbe disease (globoid cell leukodystrophy): clinical and biochemical features of 15 cases. Dev Neurosci 13: 232-239.
- Luzi P, Rafi MA, Wenger DA (1995) Characterization of the large deletion in the GALC gene found in the patients with Krabbe disease. Hum Mol Genet 4: 2335-2338.
- Luzi P, Rafi MA, Wenger DA (1996) Multiple mutations in the GALC gene in a patient with adult-onset Krabbe disease. Ann Neurol 40: 116-119.
- Rafi MA, Luzi P, Chen YQ, Wenger DA (1995) A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease. Hum Mol Genet 4: 1285-1289.
- Sakai N, Inui K, Midorikawa M, et al (1994a) Purification and characterization of galactocerebrosidase from human lymphocytes. J Biochem 116: 615-620.
- Sakai N, Inui K, Fujii N, et al (1994b) Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase. Biochem Biophys Res Commun 198: 485-491.
- Suzuki K, Suzuki Y (1970) Globoid cell leukodystrophy (KrabbeÏs disease): Deficiency of galactocerebroside b-galactosidase. Proc Natl Acad Sci USA 66: 302-309.
- Suzuki K, Suzuki Y, Suzuki K (1995) Galactosylceramide lipidosis: globoid-cell leukodystrophy (Krabbe disease). In Scriver CR, Beaudet AL, Sly WS and Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. McGraw-Hill, New York, 2671-2692.
- Svennerholm L, Vanier M-T, Manson JE (1980) KrabbeÏs disease: a galactosylsphingosine (psychosine) lipidosis. J Lipid Res 21: 53-64.
- Tatsumi N, Inui K, Sakai N, et al (1995) Molecular defects in Krabbe disease. Hum Mol Genet 4: 1865-1868.
- Wenger DA, Rafi MA, Luzi P (1997) Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Hum Mutat 10: 268-279.
- Molecular heterogeneity of Krabbe disease
Journal of Inherited Metabolic Disease
Volume 22, Issue 2 , pp 155-162
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