Biomedical subjects

R Willemsen

Publications and source records attributed to R Willemsen.

94 records · Page 6Linked to original sources

PubMedDate not supplied

Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?

In recent years there has been increased recognition of a severe perinatal lethal form of Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase. We previously reported a case of severe type 2 Gaucher disease which was seen in a medical center in Rotterdam and now present three new cases from two other families seen at the same center. Mutational analyses of these cases revealed two novel mutations, H311R and V398F, located in exons 8 and 9, respectively. The identification of four cases of lethal type 2 Gaucher disease in a single center seems to be a function of increased awareness of this phenotype, rather than of geographic clustering. The actual incidence of lethal type 2 Gaucher disease may be underestimated, as many cases may have been misclassified as collodion babies or hydrops of unknown cause.

DNA Mutational Analysis↗

PubMedDate not supplied

An immunoelectron microscopic study of glucocerebrosidase in type 1 Gaucher's disease spleen.

An immunogold labeling procedure was applied to ultrathin cryosections and used to study the subcellular localization of glucocerebrosidase in lipid-laden "Gaucher cells" in spleen from a patient with type 1 Gaucher's disease. Glucocerebrosidase protein was associated with the characteristic stored lipid material in large, irregularly shaped vacuoles. As shown by double labeling, the storage vacuoles contained not only glucocerebrosidase protein but also other lysosomal enzymes. Thus the storage vacuoles can be considered to be secondary lysosomes. The findings indicate that although glucocerebrosidase was present in secondary lysosomes in this patient, the activity of the mutant enzyme was insufficient to prevent storage of glucocerebroside in the spleen.

Adult↗

PubMedDate not supplied

Synthesis and in situ localization of lysosomal alpha-glucosidase in muscle of an unusual variant of glycogen storage disease type II.

The lysosomal alpha-glucosidase activity is reduced to 10% to 25% of the average control value in most late-onset cases of glycogen storage disease type II (GSDII). Some adult patients, however, have been identified with an exceptionally low (< 5%) residual enzyme activity. We have investigated one such unusual variant. The rate of alpha-glucosidase synthesis appeared normal but the residual enzyme activity was only approximately 3% in cultured fibroblasts, cultured muscle cells, and muscle tissue of the patient. It appeared that fully matured enzyme molecules were more abundantly present in muscle tissue than in cultured cells. The acid phosphatase activity of affected muscle fibers was enhanced due to an increased number of lysosomes. Lysosomes were particularly abundant in vacuolated areas and they contained, as judged by immunoelectron microscopy, even more alpha-glucosidase molecules than usual. An excessive amount of enzyme molecules were also observed in the endoplasmic reticulum, the site of lysosomal enzyme synthesis, and the cisternae were dilated. These observations suggest that the lysosomal system is stimulated in response to intralysosomal glycogen storage and onset of cellular injury. We hypothesize that the onset of gross pathologic abnormalities is delayed in this particular case of adult GSDII by an increased synthesis of lysosomal alpha-glucosidase, and as a consequence, an increased residual activity in storage-prone muscle fibers.

Acid Phosphatase↗

PubMedDate not supplied

FMR1 premutation allele (CGG)81 is stable in mice.

Fragile X syndrome is caused by an expansion of the CGG repeat present in the 5' UTR of the FMR1 gene. A lot has been elucidated about the genetics of the disease, but not much is known about the mechanisms involved in repeat instability. Transgenic animals with a premutation allele [(CGG)11AGG(CGG)60CAG(CGG)8] in the human FMR1 promoter were generated to study the inheritance of this repeat in mice. Three independent lines, B6, B7 and B29, in total 263 transgenic animals, were tested for repeat instability. In all meiosis and mitosis tested, the repeat inherited stably. This suggests that other factors might be important in repeat (in)stability.

Alleles↗