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Biomedical subjects

E Vamos

Publications and source records attributed to E Vamos.

At least 19 recordsLinked to original sources
PubMed1995

Frequent deletion of chromosome 19 and a rare rearrangement of 19p13.3 involving the insulin receptor gene in human ovarian cancer.

Human ovarian cancer cells usually have multiple specific chromosomal deletions which can be detected by cytogenetic analysis or molecular techniques. Tumour suppressor genes might be located in these deleted chromosomal segments. The importance of these different loci is usually estimated from the frequency with which they are deleted. Here we report a 59% loss of heterozygosity for chromosome 19 in the DNA of human invasive epithelial ovarian cancer from a series of 37 patients. In all cases informative on both chromosomal arms a subchromosomal loss is observed. Analysis of the same tumours for chromosome 17p and 11p loss suggests that loss of chromosome 19p/q is less important than 17p loss, but more important than 11p loss. The deletion of chromosome 19q seems to be associated with distant, hematogeneous metastasis (stage IV). In two patients with high grade tumours, the deletion involves a rearrangement of the insulin receptor locus (19p13.3). This suggests that some of the previously described frequent cytogenetic 19p+ markers and 19p13.3 breaks observed in high grade ovarian cancers, might actually occur in the insulin receptor gene.

Adolescent↗
PubMed1995

Severe Smith-Lemli-Opitz syndrome with prolonged survival and lipid abnormalities.

We have studied a girl with multiple congenital anomalies, growth and mental deficiency, characteristic facial anomalies, cataracts, cerebellar atrophy, and severe hypocholesterolemia. Death occurred at age 7 years. After excluding several syndromes, i.e., peroxisomal disorders, mevalonic acidaemia, and Marinesco-Sjögren syndrome, it is concluded that this girl had severe Smith-Lemli-Opitz Syndrome (SLOS) with exceptionally long survival. This diagnosis was confirmed through assay of 7-dehydrocholesterol in cultured fibroblasts.

Abnormalities, Multiple↗
PubMed1994

Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus.

Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia.

We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.

Autopsy↗
PubMed1993

Collaborative study of the molecular epidemiology of Tay-Sachs disease in Europe.

Tay-Sachs disease is a lipidosis due to the deficiency of the lysosomal hexosaminidase A. In order to understand the molecular mechanisms of this enzyme deficiency we studied 42 patients of different ethnic origins diagnosed in Europe. The strategy used consists in HEXA cDNA amplification followed by allele-specific oligonucleotide analysis for the frequent mutations, and by chemical cleavage mismatch and denaturing gradient gel electrophoresis for the detection of new mutations. 90% of alleles were clarified in this way, showing a high heterogeneity of HEXA lesions in Tay-Sachs disease. 28 different mutations were found, 20 being identified for the first time in this group of patients.

Adult↗
PubMed1992

Deletion of chromosome 11p13-11p15.5 sequences in invasive human ovarian cancer is a subclonal progression factor.

In human ovarian cancer, multiple specific chromosomal deletions can be found by cytogenetic analysis or molecular techniques such as restriction fragment length polymorphism probing. This work confirms the loss of HRAS alleles in 1 out of 2 cases of invasive ovarian cancer as determined in 32 samples or cell lines derived from 19 patients. Results with other polymorphic probes indicate that a consensus deletion probably includes 11p15.5-11p13. Tumor suppressor genes might be located in the deleted area, and deletion of the gene might then play a role in disease progression. Examination of DNA from distinct tumor sites of individual patients indicates clonal heterogeneity in the malignant cell population, indicating that loss of 11p sequences is a late event in the disease progression. Loss of alternate 11p alleles at different disease sites in one patient is inconsistent with the current model of tumor suppressor gene inactivation. The 11p deletion seems to be limited to ovarian cancers in younger patients. Eight novel permanent ovarian cancer cell lines, previously not described in the literature and derived from tumor sites from five patients, were included in the current analysis.

Adult↗
PubMed1992

Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit.

We report the molecular characterization of a case of a functional PDH-E1 (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-E1 activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-E1 alpha mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal E1 alpha cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis.

Acidosis, Lactic↗
PubMed1992

Vasopressin and gonadotropin deficiency in a boy with the ectrodactyly-ectodermal dysplasia-clefting syndrome.

A boy presented with ectrodactyly (lobster claw deformity), bilateral cleft lip and palate, semilobar holoprosencephaly and microcephaly, associated with congenital hypogonadotropic hypogonadism and central diabetes insipidus. Other aspects of pituitary function were normal. We suggest that the ectrodactyly-ectodermal dysplasia-clefting syndrome can be associated with a variety of hypothalamo-pituitary dysfunctions, in addition to the already described isolated growth hormone deficiency.

Abnormalities, Multiple↗
PubMed1992

Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA.

We have studied five children with mitochondrial myopathy manifesting within or soon after the first year of life. Muscle biopsies showed ragged-red fibers and decreased respiratory chain activity. All five patients had a severe decrease (2 to 34% of normal) in the amount of muscle mitochondrial DNA (mtDNA). The depletion of mtDNA correlated with absence of mtDNA-encoded translation products and with loss of cytochrome c oxidase enzyme activity in individual muscle fibers. This mitochondrial myopathy of childhood illustrates one phenotypic expression of a novel pathogenetic mechanism in mitochondrial diseases, the specific depletion of mtDNA in affected tissues.

Blotting, Southern↗
PubMed1992

[Collection of fetal cord blood for karyotyping].

Cordocentesis was performed in 234 pregnancies (241 fetuses) for rapid karyotyping. The indication was in 86% of cases: abnormal ultrasound. The abnormality encountered were IUGR (85 fetuses) or morphologic abnormality of the pregnancy (130 fetuses). The other indications were maternal mosaicism, mosaicism in cultured amniotic cells, maternal age (late booking), fragile X syndrome, confirmation of abnormal karyotype obtained by amniocentesis. The fetal karyotype was established in 97.5% (6 failures), 18 karyotypes were abnormal in the group "abnormal ultrasound" (208 pregnancies, 8.6%; 215 fetuses, 8.3%). No maternal complication were observed, there were 6 fetal losses (2.5%).

Blood Specimen Collection↗
PubMed1992

[Bone marrow graft in hereditary diseases].

Since 1968, bone marrow transplantation became the first line therapy for selected metabolic and immunological hereditary disorders. Actually, advances in the supportive care in bone marrow transplantation and a better knowledge of the immunology of BMT complications has been associated with a better disease correction and an increase in long term survival. New approaches are under investigation and include: hematopoietic growth factors, enzymatic replacement and gene therapy. However at the present time BMT is still the only curative treatment for selected hereditary disorders.

Bone Marrow Transplantation↗