The identification of type 1 Gaucher disease patients, asymptomatic cases and carriers in The Netherlands using urine samples: An evaluation

Aerts, Johannes M. F. G.; Miranda, María; Lacerda, Lúcia; Weely, Sonja van; Donker‐Koopman, Wilma E.; Brouwer-Kelder, B.; Jansen, D.C.; Leeuwen, Martin van; Schram, A. W.; Tsiapara, Anna; Tager, J. M.

doi:10.1016/0009-8981(91)90308-y

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…The presence of Gaucher disease was either assumed on the basis of characteristic clinical symptoms and/ or the presence of Gaucher cells in bone marrow or liver biopsies, or was investigated because of an affected sibling. The clinical diagnosis was biochemi cally confirmed by the demonstration of a markedly reduced glucocerebrosidase activity in leukocytes and/or urine samples and/or cultured skin fibroblasts (Daniels and Glew, 1982;Aerts et al, 1991).…”

Section: Materials and Methods Gaucher Patientsmentioning

confidence: 92%

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

et al. 1997

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Gaucher disease is a recessively inherited lysosomal storage disorder that is caused by a deficiency in glucocerebrosidase activity. The clinical expression is markedly heterogeneous with respect to age of onset, progression, severity, and neurological involvement. The relative incidence of glucocerebrosidase (GC) mutations has been studied extensively for Jewish but not for non-Jewish Caucasian patient populations. The present survey on mutant GC genotypes prevalent in Gaucher disease in The Netherlands was taken of 72 patients from different genetic backgrounds. This number is more than half the total number of affected Gaucher patients to be expected on the basis of the incidence of the disorder in this country. Analysis of nine GC mutations led to the identification of 74% of the mutant GC alleles in patients from 44 unrelated Dutch families (i.e., families that have lived in The Netherlands for at least several generations) and of 44% of the mutant GC alleles in patients from nine unrelated families that recently immigrated from both European and non-European countries. The N370S (cDNA 1226G) GC mutation proved to occur most frequently (41%) in the unrelated Dutch patients and less frequently (6%) in the unrelated immigrant patients and was always associated with the nonneuronopathic (Type 1) form of the disease. Apart from the association of the N370S mutation with Type 1 Gaucher disease, the prognostic value of GC genotyping was limited, since a particular GC genotype did not correlate closely to a specific clinical course, or to a specific relative responsiveness to enzyme-supplementation therapy.

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Section: Materials and Methods Gaucher Patientsmentioning

confidence: 92%

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

et al. 1997

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“…The clinical diagnosis was biochemically confirmed by the demonstration of a markedly reduced glucocerebrosidase activity in leukocytes and/or urine samples and/or cultured skin fibroblasts (Daniels and Glew, 1982;Aerts et al, 1991).…”

Section: Materials and Methods Gaucher Patientsmentioning

confidence: 99%

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

et al. 1997

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“…Fractionation of GM95 cells and separation of ER and Golgi membranes on sucrose gradients was performed as described ( Burger et al, 1996 ). β-Galactosidase and β-hexosaminidase activity in cell lysates and media were analyzed according to Galjaard (1980) and Aerts et al (1991) . L-DOPA oxidase activity of tyrosinase and TRP-1 was detected by zymography of 10% SDS-PAA gels run in nonreducing Laemmli sample buffer ( Jimenez-Cervantes et al, 1993b ).…”

Section: Methodsmentioning

confidence: 99%

Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex

Sprong

Degroote

Claessens

et al. 2001

The Journal of Cell Biology

123

133

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A;lthough glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.

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The identification of type 1 Gaucher disease patients, asymptomatic cases and carriers in The Netherlands using urine samples: An evaluation

Cited by 4 publications

References 22 publications

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value

Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex

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