Search PubMed⌕ Search

Biomedical subjects

E Passarge

Publications and source records attributed to E Passarge.

At least 55 records · Page 3Linked to original sources
PubMed1990

Use of the RB1 cDNA as a diagnostic probe in retinoblastoma families.

Use of an intragenic BamHI restriction fragment length polymorphism within the 5' end of the retinoblastoma gene (RB1) provided improved genetic counselling for five familial and ten non-familial retinoblastoma patients and their relatives. All other polymorphic probes within RB1 were uninformative in three families, and accuracy of diagnosis was improved by use of this polymorphism in two families. In 10/14 informative constitutional DNA-RB tumor DNA pairs, a reduction to homozygosity allowed identification of the RB1 allele at risk to carry a germline RB1 mutation.

Child↗
PubMed1990

Somatic mosaicism in a patient with bilateral retinoblastoma.

We describe two cell lines with different deletions of the retinoblastoma gene in a patient with bilateral retinoblastoma. This patient has transmitted the mutation less frequent in his lymphocytes to two affected children. We cloned, mapped, and sequenced the junction fragments of the two deletions and found that they share one breakpoint but extend into opposite directions. An insertion of 4 bp of unknown origin is present between the breakpoints in one of the deletions. The second deletion shows a more complex rearrangement, including an inversion at the 5' end. Short regions of homology were found at the breakpoints and flanking the inversion. These results support the notion that bilateral retinoblastoma may not only be due to a germ-line mutation but also to a postzygotic mutation leading to somatic mosaicism.

Base Sequence↗
PubMed1989

Further delineation of the Nijmegen breakage syndrome.

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a "bird-like" face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.

Abnormalities, Multiple↗
PubMed1989

Maternal origin of a de novo chromosome 8 deletion in a patient with Langer-Giedion syndrome.

The anonymous DNA probe L32, which defines the D8S48 locus within the Langer-Giedion syndrome chromosome region on the long arm of chromosome 8, was used to search for a common restriction fragment length polymorphism. A HindIII and an MspI polymorphism were detected (polymorphism information contents 0.25 and 0.19, respectively). Both polymorphisms were informative in the family of a Langer-Giedion patient carrying a de novo interstitial deletion 8q23-24.1. Lack of transmission of a maternal haplotype indicates that this deletion occurred during maternal gametogenesis. This finding contrasts with the frequent paternal origin of mutations in other microdeletion syndromes.

Chromosome Banding↗
PubMed1989

Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma.

Epigenetic models for tumor formation assume that oncogenic transformation results from changes in the activity of otherwise normal genes. Since gene activity can be inhibited by DNA methylation, and inactivation of tumor suppressor genes is a fundamental process in oncogenesis, we investigated the methylation status of the retinoblastoma suppressor gene (RB gene) on chromosome 13, in blood and tumor cells from 21 retinoblastoma patients. Using methylation-sensitive restriction enzymes and a cloned DNA probe for the unmethylated CpG island at the 5' end of RB gene, we obtained evidence of hypermethylation of this gene in a sporadic unilateral retinoblastoma tumor. The closely linked esterase D gene and a CpG-rich island on chromosome 15 were not affected. We suggest that changes in the methylation pattern of the RB gene play a role in the development and spontaneous regression of some retinoblastoma tumors.

DNA Restriction Enzymes↗
PubMed1989

Mechanism of i(6p) formation in retinoblastoma tumor cells.

Isochromosome (6p) represents a highly characteristic cytogenetic abnormality of human retinoblastoma (RB) cells and may be important for tumor progression. To elucidate the mechanism by which this abnormal chromosome is formed, 24 RB tumors and three cell lines were studied by means of DNA polymorphisms specific for the short arm and the long arm of chromosome 6. Our results indicate that mitotic nondisjunction leading to trisomy 6 precedes the isochromosome formation. The isochromosome may then be formed by transverse division of the centromere or intrachromosomal chromatid exchange.

Alleles↗
PubMed1989

Bloom's syndrome. XII. Report from the Registry for 1987.

Bloom's syndrome has been known as a clinical entity for 34 years. Careful records of cases diagnosed throughout the world have been maintained since its recognition as an entity, and most instances of cytologically verified Bloom's syndrome have been accessioned to what has been referred to as the Bloom's Syndrome Registry since the mid-1960s. Presented here is the fourth in a series of progress reports from the Registry of information accumulated during this long-term surveillance of affected families, along with mention of selected recent advances that have been made in the understanding of the syndrome. 130 persons had been accessioned to the Registry by the end of 1987; 96 of these were alive, their mean age being 18.9 years. Although a number of clinical complications occur in Bloom's syndrome, the most important is malignant neoplasia. In the 130 persons in the Registry, 57 malignant neoplasms had been detected, the mean age at diagnosis being 24.8 years. Neoplasia in Bloom's syndrome is noteworthy not only because of its frequency and exceptionally early age of emergence but for its variety of histological types and sites of origin.

Adolescent↗
PubMed1988

HLA-A,B,C,DR typing and 17-OHP determination for second trimester prenatal diagnosis of 21-hydroxylase deficient CAH.

In 18 families at risk for the HLA-linked, 21-hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA-A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17-hydroxyprogesterone (17-OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation. In 16/18 families, both HLA typing of AFC and 17-OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17-OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a 'missed' HLA antigen in one case and to serologically cross-reactive HLA antigens in the second. Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17-OHP measurement was not performed in one family and in the second family the 17-OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus. In conclusion, a combination of HLA typing of cultured AFC and 17-OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA-DR typing of AFC as presented here for the first time proved helpful in families with HLA-A,B homozygosity due to parental sharing of antigens and can be informative for identifying HLA-B/21-OH recombinant haplotypes.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Construction of a chromosome 15-specific linking library and identification of potential gene sequences.

We have tested a strategy for the construction of a total restriction fragment map of a human chromosome and the rapid isolation of a great number of genes from a specific chromosome. The strategy is based on the cloning of chromosome-specific CpG-rich DNA sequences which are present at the 5' end of many genes. This approach has two important implications: (i) the clones can be used to probe pulsed-field gradient gel blots and link restriction fragments generated by CpG restriction endonucleases, and (ii) the finding of tight genetic or physical linkage between one of these gene probes and a given hereditary disease would make the marker a good candidate gene for this disease. We have constructed a chromosome 15-specific linking library and identified potential gene sequences.

Base Sequence↗
PubMed1988

Application of linkage analysis to genetic counselling in families with hereditary retinoblastoma.

Six families with retinoblastoma in more than one member were investigated with DNA markers linked to the retinoblastoma locus because direct analysis had not disclosed the gene defect. In all of the families we could identify the affected chromosome and predict the genetic risk with a high level of confidence (90 to 99%). In one patient the test helped to detect tumour development earlier than usually possible. Several subjects were found not to carry a mutation, thus obviating frequent ophthalmological examinations under anaesthesia as would be necessary otherwise. These results show that linkage analysis can be successfully applied to genetic counselling in families with hereditary retinoblastoma.

Adult↗
PubMed1988

Pachytene analysis in males heterozygous for a familial translocation (9;12;13) (q22; q22; q32) ascertained through a child with partial trisomy 9.

A family with four male and three female heterozygotes for a three-way translocation (9;12;13) (q22; q22; q32) in three generations was ascertained through a chromosomally imbalanced newborn with an additional derivative chromosome 9 resulting from nondisjunction. Three heterozygous males from two generations with apparent differences in their fertility status were investigated using pachytene spreads and testicular histology. Pachytene analysis in all three individuals, the fertile (II-2) as well as the subfertile (III-7) and infertile (III-9), showed a hexavalent with central nonpairing around the translocation breakpoints in nearly all spermatocytes. Thus, the observed hexavalent configurations in pachytene do not seem to have caused impaired fertility. This rather may have been the result of sperm carrying unbalanced chromosome sets. However, the observed difference in fertility between the heterozygous fertile male in generation II and his two heterozygous sons remains unexplained.

Chromosome Banding↗
PubMed1987

Detection of submicroscopic deletions and a DNA polymorphism at the retinoblastoma locus.

DNA samples from 60 unrelated patients with retinoblastoma were screened by Southern blot hybridization using two probes that are closely linked to the retinoblastoma locus within human chromosome band 13q14. Seven of 44 patients with bilateral or multifocal unilateral retinoblastoma and one patient with unifocal unilateral retinoblastoma were found to have a heterozygous deletion for the anonymous DNA sequence H3-8. Three of the eight deletions did not include the esterase D locus and were undetectable by conventional cytogenetic analysis. The findings are compatible with the deletions being the cause of retinoblastoma in these cases and provide a basis for DNA diagnosis in nearly 20% of patients with bilateral and multifocal unilateral retinoblastoma. The H3-8 probe also detects a restriction fragment length polymorphism that is a useful genetic marker in some families.

Child↗
PubMed1985

Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: a new autosomal recessive disorder.

We describe nine patients with an apparently new genetic disorder characterized by: microcephaly with normal intelligence; "bird"-like facial appearance; cellular and humoral immune defects; and increased risk for lymphoreticular malignancies. The postmortem findings of five patients are described. Chromosome instability appears not to be a component of the disorder. The occurrence in three pairs of sibs and isonomy in another family suggests autosomal recessive inheritance.

Child↗