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H Scheffer

Publications and source records attributed to H Scheffer.

At least 73 records · Page 4Linked to original sources
PubMed1994

A giant congenital orbital tumor: an unusual presentation of retinoblastoma.

We report a case of an unusual giant congenital tumor presenting in a newborn infant as a large exophytic mass emerging from the left orbit. After enucleation orbital recurrence developed within 14 days. No anti-tumor treatment was given and the child died at the age of 4 weeks. The histopathological and cytogenetical analysis of the tumor is presented. The tumor was diagnosed as a retinoblastoma but we could not exclude the possibility of a neuroblastoma.

Eye Neoplasms↗
PubMed1994

Apparent SMA I unlinked to 5q.

A proband with a clinical picture indistinguishable from SMA type I is described. The parents are second cousins. On DNA analysis it appeared that the proband and his healthy 2 year old sib had inherited the same haplotypes for DNA markers flanking the SMA locus on 5q. This supports non-linkage of SMA to chromosome 5q in this family. The consanguinity of the parents raises the possibility of a second locus for autosomal recessive SMA type I outside the 5q12-13 region. This may have implications for genetic counselling after prenatal diagnosis in consanguineous families. Furthermore, this case illustrates the importance of the inclusion of all healthy sibs in prenatal DNA studies for SMA type I.

Chromosomes, Human, Pair 5↗
PubMed1994

A deletion hybrid breakpoint map of the chromosomal region 13q14-q21 orders 19 genetic markers in 10 intervals.

A deletion hybrid breakpoint map of the chromosomal region 13q14-q21 has been constructed using 19 DNA markers and 13 cell lines with breakpoints in this chromosomal region. The cell lines define 10 distinct intervals in this region, which spans approximately 20 Mb. The markers include 6 RFLP markers, 11 microsatellites that provisionally had been mapped to the region 13q14-21, and 2 new polymorphic CA-repeats that were developed from an EMBL3 library of cell line ICD, containing 13pter-q14.3. The following order of markers was established: CEN-D13S320-(D13S118, D13S153)-RB1-D13S319-D13S25-(D13S31, D13S59, D13S133, D13S137)-D13S163-D13S119-(D13S26, D13S55)-(D13S131, D13S134, D13S135, D13S144, D13S152)-TEL.

Base Sequence↗
PubMed1994

Tissue kallikrein activity and kinin release in human endothelial cells.

The kininogenase, tissue kallikrein (EC 3.4.21.8), has been identified in different blood vessels. The enzyme was mainly found in vascular smooth muscle cells. It is not known whether it is present and functionally active in vascular endothelial cells. The following study investigates the presence of tissue kallikrein in endothelial cells from human umbilical veins and pulmonary arteries. Tissue kallikrein was demonstrated in three ways: 1) by immunostaining in endothelial cells; 2) by measurement of tissue kallikrein activity using a colorimetric assay; 3) by the measurement of kinin release in intact and homogenised endothelial cells with a radioimmunoassay. Immunostaining demonstrated the presence of tissue kallikrein in endothelial cells from human umbilical veins and endothelial cells from human pulmonary arteries. Tissue kallikrein-like activity, measured by the degradation of D-Val-cyclohexyl-Ala-Arg-4-nitraniline, was 3.57 +/- 0.5 mU/10(6) endothelial cells from human umbilical veins and 7.52 +/- 0.84 mU/10(6) endothelial cells from human pulmonary arteries. Intracellular kinin concentrations were 424 +/- 83 pg/10(6) cells in endothelial cells from human umbilical veins and 576 +/- 146 pg/10(6) cells in endothelial cells from human pulmonary arteries, and they increased in a time-dependent manner after homogenisation. The increase was abolished by aprotinin (1000 kIU), an inhibitor of tissue kallikrein in both cell types. Addition of exogenous kallikrein (5 mU) to homogenised cells led to a five fold increase of kinin concentrations after five minutes, indicating a sufficient resource of cellular kininogen. Removal of extracellularly bound kininogen by washing with dextran sulphate (100 mg/l) resulted in an approximately 75% reduction of the cellular kinin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

Physical localisation of the chromosomal marker D13S31 places the Wilson disease locus at the junction of bands q14.3 and q21.1 of chromosome 13.

D13S31 is the marker closest to the Wilson disease locus according to genetic analysis. Its physical localisation was refined by fluorescent in situ hybridisation to the junction to chromosomal bands 13q14.3 and 13q21.1. Using polymerase chain reaction analysis, D13S31 and D13S59 (the closest proximal and distal marker, respectively) were found to be located on the end of the der(13) consisting of 13pter-13q14.3: in the somatic cell hybrid ICD, and to be absent from the cell lines WC-H38B3B6 containing a del(13) (13pter-q13::13q21.1-qter) and KSF39 containing a del(13) (13pter-q14.1:).

Animals↗
PubMed1993

Linkage and apparent heterogeneity in proximal spinal muscular atrophies.

Linkage studies with 9 highly informative DNA markers on the long arm of chromosome 5 were performed in 12 multiplex families (29 patients) with spinal muscular atrophy (SMA) from The Netherlands. The results of the linkage analysis were compatible with localization of a major SMA gene in the chromosomal region 5q12-13. By minimum recombinant analysis the most likely position of the SMA locus was between loci D5S6/D5S125 and D5S112/MAP1B, which is in agreement with several linkage studies from other countries. In four families, however, more than one crossover between SMA and a flanking DNA marker appeared, and in one family the observed hybridization phenotype for the markers closely flanking the SMA locus was identical for an unaffected individual and for his two affected sibs with SMA type III. For this latter family, among several explanations the most likely are either the presence of a double crossover or linkage heterogeneity.

Chromosome Mapping↗
PubMed1993

Confirmation of clinical diagnosis in requests for prenatal prediction of SMA type I.

The recent discovery of a major SMA-locus in the chromosomal region 5q makes it possible to carry out prenatal DNA studies in families in which a child with SMA type I has been born. Since direct mutation analysis is not yet possible, the reliability of prenatal prediction of SMA type I usually depends on the certainty of the clinical diagnosis in the index patient. Sixteen requests were received for DNA studies in couples who had had a previous child with SMA type I. After re-evaluation, the performance of prenatal diagnosis was rejected in four cases. Among the other twelve families prenatal DNA analysis of chorion villus biopsies has been carried out in three families. In all three cases the fetus had inherited the high-risk haplotypes from both parents, and the parents chose to terminate the pregnancy. An illustration of the prenatal DNA studies in one family is given. The importance of confirmation of the diagnosis SMA type I before performing DNA studies is emphasised.

Biopsy↗
PubMed1992

Analysis of a metastasizing testicular mixed gonadal stromal tumor with osteosarcoma components suggests that a malignant tumor with the histology of osteosarcoma may develop without primary involvement of RB1 and TP53.

A malignant stromal tumor of the testis with an osteosarcoma component and five of its metastases mainly containing osteosarcoma have been analyzed for RB1 and TP53 abnormalities. Whereas in the primary tumor and in some of the metastases loss of heterozygosity could not be detected for RB1 or for the 17p13 region in which TP53 is located, other metastases showed such losses of heterozygosity. By polymerase chain reaction analysis an 18-base pair deletion from exon 5 of the TP53 gene was found in a small proportion of primary tumor cells and in one of the metastases, but not in the other metastases. Therefore, in this case neither RB1 nor TP53 seems to play an essential role in the initiation of osteosarcoma.

Amino Acid Sequence↗
PubMed1992

Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma.

A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)] has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the derivative chromosome 2 or the derivative chromosome 13 without a normal chromosome 13 homologue. Ten linked DNA probes known to be located within bands 13q13-q14 were mapped relative to the breakpoint on chromosome 13, allowing localization of the breakpoint region between two loci separated by 5.5 cM. A long-range restriction map extending approximately 2,300 kb around these loci failed to provide evidence of rearrangement. Additionally, we confirmed that the FMS-like tyrosine kinase gene (FLT), previously localized to 13q12 by in situ hybridization, is located proximal to the breakpoint, and we demonstrated that FLT is not a target for disruption by this tumor-specific translocation.

Blotting, Southern↗
PubMed1992

Prenatal diagnosis in a family with X-linked chronic granulomatous disease with the use of the polymerase chain reaction.

In the X-linked form of chronic granulomatous disease (X91 degrees CGD), the genetic defect is linked to the CYBB locus on the X chromosome. We studied a family with a genetic defect in this gene, consisting of a G----A substitution at the fifth base of the 5' donor splice site of intron 3. This mutation leads to skipping of exon 3 after transcription of the gene. The expectant mother was diagnosed as a carrier. Analysis of polymerase chain reaction (PCR)-amplified genomic DNA from a chorionic villus biopsy (CVB) showed the same mutation in the male fetus. After termination of the pregnancy, the diagnosis was confirmed by conventional methods. This is the first time that PCR has been used for prenatal diagnosis of CGD.

Abortion, Eugenic↗
PubMed1992

Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. A minimum recombinant analysis using D13S22, ESD, RB1, D13S31, D13S55, D13S26, D13S39, and D13S12, all localized at 13q14-q22, has been carried out in 20 WD families of Northwest-European origin. No inconsistencies have been observed with respect to locus order or location of the WD locus (WND) compared with previous linkage studies. D13S31 was mapped as the closest marker proximal to WND, whereas D13S55 and D13S26 were mapped as the closest markers distal to WND. We have identified a crossover between WND and D13S31 in one family and a crossover between WND and D13S55 in another. These crossover sites can be used as reference points for new chromosome 13q14-q21 markers, and are therefore important for a more accurate mapping of the WD locus.

Chromosome Mapping↗
PubMed1992

[Carrier detection in cystic fibrosis. Various illustrative examples].

Until 1989 carrier detection in families with cystic fibrosis (CF) took place by means of linkage analysis with polymorphic DNA markers. This is an indirect method to demonstrate carriership. For linkage analysis it is often essential that there is patient material available. Since the identification of the CF gene, direct DNA analysis of the most frequent CF mutations is possible. This allows direct demonstration of carriership by means of DNA analysis in the majority of cases, without the necessity always to investigate family members. Carriership detection of persons not related to CF patients, for example partners of CF carriers, is with this method also possible. In cases where none of the frequent CF mutations can be found, linkage analysis may still prove helpful. In this article we demonstrate some clinical examples of carrier investigation.

Child, Preschool↗
PubMed1991

Consanguinity sans reproche.

In a family with two cystic fibrosis (CF) patients and consanguineous parents, DNA analysis showed that the CF in the children was not caused by homozygosity by descent, since two different mutations were involved. A formula is given for calculating the probability that parental consanguinity, if it exists, is causally related to the existence of an autosomal recessive disease in affected children.

Alleles↗
PubMed1991

Partial 3q duplication syndrome and assignment of D3S5 to 3q25-3q28.

We report a girl with a de novo duplication of the distal part of the long arm of chromosome 3 and review the literature. Our patient had the facial characteristics and many other anomalies of the partial 3q duplication syndrome. As a hitherto undescribed symptom in partial 3q trisomy syndrome, she had microphthalmia. The karyotype of this girl was interpreted as an inverse duplication of the terminal portion of chromosome 3: 46,XX,inv dup (3)(pter-q28::q28-q25::q28-qter). Quantitative hybridisation studies with 3p and 3q probes gave a consistent 3:2 ratio of the relative intensities of the q bands in relation to the p bands between patient and control. This confirmed the presence of a 3q duplication and delineated the location of D3S5 to 3q25-3q28.

Blotting, Southern↗
PubMed1991

Complete association of loss of heterozygosity of chromosomes 13 and 17 in osteosarcoma.

Mutations of the retinoblastoma (RB1) gene are not confined to retinoblastoma, but are also involved in the development of osteosarcoma. Structural aberrations within the RB1 gene have been studied in fresh samples of eleven cases of osteosarcoma. In five cases a rearrangement was detected, one of which was best explained as a partial duplication. The chromosomal mechanisms by which the nonmutated RB1 allele was lost appeared to be similar in frequency to those that have been reported for retinoblastoma. Loss of heterozygosity was observed for chromosomes 3, 11, 13, 17, and 22. However, when no loss of heterozygosity of chromosome 13 was detected, the other chromosomes retained their heterozygosity as well. A complete association of loss of heterozygosity of chromosomes 13 and 17 was observed. This can be taken as an indication of the involvement of another tumor suppressor gene at chromosome 17 in the initiation of osteosarcoma.

Adolescent↗
PubMed1990

[Carrier detection in relatives of patients with cystic fibrosis and their partners].

In the clinical genetics centres of Groningen and Rotterdam carrier detection by means of DNA analysis was performed in 55 relatives of cystic fibrosis patients at their request; 32 of them were siblings, 22 were uncles and aunts, and one was a first cousin. In 31 of them carriership could be demonstrated. Carrier detection was also performed in 23 of their partners, in 3 partners of female CF patients, and in 4 AI donors. In one of the partners of the carriers carriership was demonstrated also. This is the first couple in The Netherlands to whom information on the 25% risk of CF in a future child and on the corresponding reproductive options could be given prior to the birth of a first affected child. Since not all mutations of the CF gene are detectable with present methods, carrier detection still has its restrictions, which are discussed.

Adult↗