Publications by authors named "Victor H Garritsen"

4 Publications

  • Page 1 of 1

Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk.

Prenat Diagn 2007 Dec;27(12):1133-7

Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Objective: Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977.

Methods: UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of (3)H-thymidine.

Results: XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads.

Conclusion: Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.1849DOI Listing
December 2007

Prenatal diagnosis of the Cockayne syndrome: survey of 15 years experience.

Prenat Diagn 2006 Oct;26(10):980-4

Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Objective: Evaluation of results in a consecutive series of 29 prenatal diagnoses for the Cockayne syndrome.

Methods: Recovery of DNA-synthesis in UV-irradiated cultured fetal cells was measured by scintillation counting of incorporated (3)H-thymidine. Semiquantitative autoradiographic assessment of the recovery of RNA-synthesis (RecRS) was used as an adjunctive method.

Results: In 26 of the 29 pregnancies at risk, a definite diagnosis was directly made, based on normal (n = 23) or clearly reduced (n = 3) recovery of DNA-synthesis in UV-irradiated cultured chorionic villus (CV) cells (n = 23) or amniocytes (n = 3). Adjunctive studies were performed in several pregnancies to corroborate the initial results. On three occasions initial results were unreliable, which required investigation of the recovery of RNA-synthesis (n = 2) or even additional amniocentesis (n = 1) to achieve a firm diagnosis. Thus, four affected fetuses were diagnosed in 29 pregnancies at risk (13.8%).

Conclusion: Reliable prenatal diagnosis of the Cockayne syndrome can be made by the demonstration of a strongly reduced recovery of DNA-synthesis in UV-irradiated cultured chorionic villus cells or amniocytes. Assessment of the recovery of RNA-synthesis was needed as an adjunctive method in rare cases of poor cell growth and DNA-synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.1541DOI Listing
October 2006

Prenatal diagnosis of citrullinemia and argininosuccinic aciduria: evidence for a transmission ratio distortion in citrullinemia.

Prenat Diagn 2006 Mar;26(3):242-7

Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.

Background: In the course of 25 years, we have experienced a high rate of affected fetuses in the prenatal diagnosis of citrullinemia.

Methods And Results: Ninety-one pregnancies at 1 in 4 risk were tested; 36 were diagnosed as affected (39.5%; P = 0.0015). The high rate of positive diagnoses was found both after chorionic villus sampling (24/68 = 35.3%) and amniocentesis (12/23 = 52.2%) despite the completely different and independent techniques used. Using exactly the same (indirect) enzyme assay for argininosuccinic aciduria on chorionic villi and a similar method on amniotic fluid, the expected rate of affected fetuses was found: 13/53 = 24.5%. Technical and genetic causes for the unexpected results were excluded by confirmatory studies performed on independent fetal material, which was available for 27 of the 36 fetuses affected with citrullinemia. Biochemical confirmation was obtained in the 27 cases, whereas in 18 fetuses homozygosity or compound heterozygosity for disease-causing mutations were retrospectively demonstrated in the stored fetal cells.

Conclusion: The results suggest the occurrence of preferential transmission of the mutant allele. An explanation for this phenomenon may be found in a protective role of argininosuccinic acid synthetase deficiency in mutant sperm cells against the possibly detrimental or apoptotic effect of nitric oxide produced normally from arginine by nitric oxide synthase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.1390DOI Listing
March 2006

Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients.

Proc Natl Acad Sci U S A 2002 Jan 2;99(2):815-20. Epub 2002 Jan 2.

Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom.

Xeroderma pigmentosum variant (XP-V) cells are deficient in their ability to synthesize intact daughter DNA strands after UV irradiation. This deficiency results from mutations in the gene encoding DNA polymerase eta, which is required for effecting translesion synthesis (TLS) past UV photoproducts. We have developed a simple cellular procedure to identify XP-V cell strains, and have subsequently analyzed the mutations in 21 patients with XP-V. The 16 mutations that we have identified fall into three categories. Many of them result in severe truncations of the protein and are effectively null alleles. However, we have also identified five missense mutations located in the conserved catalytic domain of the protein. Extracts of cells falling into these two categories are defective in the ability to carry out TLS past sites of DNA damage. Three mutations cause truncations at the C terminus such that the catalytic domains are intact, and extracts from these cells are able to carry out TLS. From our previous work, however, we anticipate that protein in these cells will not be localized in the nucleus nor will it be relocalized into replication foci during DNA replication. The spectrum of both missense and truncating mutations is markedly skewed toward the N-terminal half of the protein. Two of the missense mutations are predicted to affect the interaction with DNA, the others are likely to disrupt the three-dimensional structure of the protein. There is a wide variability in clinical features among patients, which is not obviously related to the site or type of mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.022473899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC117388PMC
January 2002