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E Seemanová

Publications and source records attributed to E Seemanová.

At least 19 recordsLinked to original sources
PubMed1998

Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Cells from NBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from ataxia telangiectasia. We describe the positional cloning of a gene encoding a novel protein, nibrin. It contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain. A truncating 5 bp deletion was identified in the majority of NBS patients, carrying a conserved marker haplotype. Five further truncating mutations were identified in patients with other distinct haplotypes. The domains found in nibrin and the NBS phenotype suggest that this disorder is caused by defective responses to DNA double-strand breaks.

Amino Acid Sequence↗
PubMed1998

[DNA diagnosis of the fragile X chromosome syndrome--FRAXA using PCR].

BACKGROUND: Fragile X syndrome is gonosomal recessive mental retardation with the frequency 1:1000 in male population. Fragile X syndrome is caused by amplification of CGG repeat in 1. exon of FMT-1 gene. The aim of this study was to set up and validate a rapid and efficient PCR diagnosis to select FRAXA negative patients in population of mental retarded patients. METHODS AND RESULTS: In the set up phase of the method, 196 patients were diagnosed. We were using modified radioactive PCR of CGG. Obtained PCR fragments were separated on 6% denaturing PAGE. Results were correlated with Southern blot analysis using pE5.1 probe. STR-PCR was verified on a large set of patients and shows validity and efficiency of results in the case of pre- and full mutations in male hemizygous patients too. For estimation of carriers with pre- and full mutation by females modified diagnostic approach was developed. There was no difference found between results from PCR and Southern blot analysis. CONCLUSIONS: The PCR method is convenient not only for selection of FRAXA negative patients, but for diagnosis of full mutation and premutation of affected probands.

Chromosome Fragility↗
PubMed1997

The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21.

Nijmegen breakage syndrome (NBS; Seemanová II syndrome) and Berlin breakage syndrome (BBS), also known as ataxia-telangiectasia variants, are two clinically indistinguishable autosomal recessive familial cancer syndromes that share with ataxia-telangiectasia similar cellular, immunological, and chromosomal but not clinical findings. Classification in NBS and BBS was based on complementation of their hypersensitivity to ionizing radiation in cell-fusion experiments. Recent investigations have questioned the former classification into two different disease entities, suggesting that NBS/BBS is caused by mutations in a single radiosensitivity gene. We now have performed a whole-genome screen in 14 NBS/BBS families and have localized the gene for NBS/BBS to a 1-cM interval on chromosome 8q21, between markers D8S271 and D8S270, with a peak LOD score of 6.86 at D8S1811. This marker also shows strong allelic association to both Slavic NBS and German BBS patients, suggesting the existence of one major mutation of Slavic origin. Since the same allele is seen in both former complementation groups, genetic homogeneity of NBS/BBS can be considered as proved.

Alleles↗
PubMed1996

X-linked microcephaly, microphthalmia, microcornea, congenital cataract, hypogenitalism, mental deficiency, growth retardation, spasticity: possible new syndrome.

We describe a male and his sister's son with microcephaly, microphthalmia, microcornea, congenital cataract, hypogenitalism, severe mental deficiency, progressive spasticity and growth retardation. Both affected males have brachycephaly, upslanting palpebral fissures, epicanthal folds, highly arched palate, small mouth, and retrognathia. Two maternal cousins of the propositus's mother may also have been affected. Chromosomal and metabolic findings in the propositus were normal. To our knowledge, this disorder has not been reported before as an X-linked syndrome.

Cataract↗
PubMed1996

[A method for detection of germinal mutations in the p53 tumor suppressor gene].

BACKGROUND: The tumour suppressor gene p53 is exhibits somatic mutations in a high proportion of human tumours. In addition, there are cancer families suffering from the Li-Fraumeni syndrome, the members of which carry germ line mutations in this gene. The carriers of the p53 germ line mutations have a high risk of developing tumours. The genetic diagnosis of carriership of the mutation in the tumour family members is important for preventive measures and for eventual tumour therapy modification. METHODS AND RESULTS: We have developed a method for the detection of germ line mutations in the p53 gene based on non-radioactive SSCP and direct sequencing of PCR products. We have proved the efficiency of the method by finding known mutations in eight tumour cell lines. In our collection of tumour families we have detected polymorphisms in exons 4 and 6 of the p53 gene. In one family which conformed to the criteria of the Li-Fraumem syndrome we have found a novel germ line mutation in exon 5. CONCLUSIONS: The method developed by us is very simple and sensitive. The germ line mutations in the p53 gene are very rare.

Female↗
PubMed1992

Autosomal dominant insulin resistance syndrome due to postbinding defect.

We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin-resistant diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a preclinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer.

Acanthosis Nigricans↗
PubMed1992

[Personal experience with genetic study of the hearing-impaired].

In 1988-1990 the authors examined on account of impaired hearing in the family 78 families, which were divided into two groups. The first group comprises 48 families of actively invited pupils from schools with children with impaired hearing in Prague, the second group comprises 30 families examined in the framework of common counselling and consultation services. On the first group a genetic aetiology of the disorder was revealed in 75% and in the second group in 73.3% of the cases. An autosomal recessive type of heredity was proved unequivocally in 31.3% in group 1 and in 20.0% in group 2. An autosomal dominant type of heredity was found in 6.25% in group 1 and in 6.7% in group 2. X-linked deafness was proved only in group 1 in 4.2% and sporadic syndromes only in group 2 in 13.3%. In 33.3% in both groups it was not possible to differentiate the type of heredity (most frequently the child and both parents were affected). In the first group three genetic syndromes were detected and in group 2 seven genetic syndromes. As the percentage of genetically conditioned hearing disorders in both groups is relatively high, the authors consider active screening of deaf children more useful so far.

Child↗
PubMed1992

[Screening for fragile X syndrome in handicapped boys].

From a group of 201 mentally retarded boys 149 were clinically and somatometrically examined. Chromosomal analysis for detection of a fra(X)-syndrome was undertaken, when more than 3 of the chosen examination parameters were suspicious or when anamnestic clues for X-chromosomally linked mental retardation were present. 89 boys fulfilled above requirements, 14 of these had a fra(X)-syndrome (15.7%). The following symptoms were found with outstanding frequency: hyperactivity, hypotonic muscles, enlargement of testes, increased length of hands, retarded development of speech, dermatoglyphic abnormalities. If more than 3 of these findings occur, a chromosomal analysis for exclusion of a fra(X)-syndrome should be performed.

Child↗
PubMed1992

Clinical and biochemical characterization of syndromes associated with defects of the insulin receptor.

During 3 years of collaboration we have detected 13 patients with insulin resistance syndromes among the 800 patients referred to our genetic counseling center for diagnosis during that time. It represents about 1.5% of all diagnostic problems of our genetic counseling center. Thus it seems to us that insulin receptor disorders are not as rare as previously appreciated. We describe here the clinical and biochemical findings of four of them as well as characteristics of disorders of insulin receptors. On cellular level these four patients represents the full scale of insulin receptor defects and demonstrate genetic heterogeneity of these disorders.

Adolescent↗
PubMed1992

Studies on cultured fibroblasts from patients with cutaneous malignant melanoma.

Cultured fibroblasts from patients with cutaneous malignant melanoma (CMM) were tested for chromosomal instability by determination of micronuclei (MN) and sister chromatide exchange (SCE). The constitutive as well as the UV-induced level of MN was increased in CMM patients, being most pronounced in the familial cases. There was an increased UV sensitivity in CMM by using SCE, but no spontaneously enhanced SCE value. The enhanced UV sensitivity in CMM patients was in a comparable range as those of XP heterozygotes. We thus conclude that chromosomal instability is a concurrent feature of a genetic predisposition for CMM.

Cells, Cultured↗
PubMed1991

Duffy locus linkage and HLA antigens in hereditary motor-sensory neuropathy.

The Duffy system, Fya, Fyb, and HLA antigens were studied in 86 members, 39 affected, 47 healthy subjects, of 17 families with HMSN types I, II and III. The incidence of autosomal dominant as well as recessive, or sporadic forms was registered. In the autosomal dominant form of HMSN type I a close linkage was found between the genes coding the disease under study and the determinants Fya and Fyb. Recombination was found in only 9.1% of the cases. A study of HLA antigens revealed a major decrease in antigen B27 in the patients under scrutiny. An identical haplotype of most of the parents was a conspicuous feature in families with the autosomal dominant form of HMSN type I.

Adolescent↗
PubMed1990

First-trimester prenatal diagnosis of the Nijmegen breakage syndrome and ataxia telangiectasia using an assay of radioresistant DNA synthesis.

Prenatal diagnosis was performed in two pregnancies at risk of the Nijmegen breakage syndrome. In one pregnancy, an affected fetus was diagnosed by demonstration of radioresistant DNA synthesis, using autoradiographic detection of incorporated tritiated thymidine in cultured chorionic villus cells. The diagnosis was confirmed in fetal skin fibroblasts. In the other case, the fetus appeared unaffected. Using the same procedure, unaffected fetuses were predicted from chorionic villus cells in two pregnancies at risk of ataxia telangiectasia, which is another genetic disorder showing the feature of radioresistant DNA synthesis. The present biochemical method for prenatal detection of Nijmegen breakage syndrome and ataxia telangiectasia can be used as a simplified alternative to the cytogenetic procedures reported earlier for ataxia telangiectasia.

Ataxia Telangiectasia↗
PubMed1990

An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal intelligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability.

We have collected and studied the genealogical data of 8 patients with the autosomal recessive syndrome of microcephaly, normal intelligence, immunodeficiency, risk of malignancy and chromosomal instability resembling ataxia telangiectasia (AT), but different in complementation group. 50% of our probands died from lymphoreticular malignancies in early childhood. We have found a significantly increased incidence of malignant tumors in 142 blood relatives as compared with a control group of 87 spouses. All patients belonged to the same complementation group differing from the 5 known AT complementation groups, which seems to be in general more malignant than all other groups of AT. From this standpoint our material is homogeneous in contrast to other similar studies in AT families. We think this syndrome represents another model to examine the relationship between genetic background, chromosomal abnormalities, immunodeficiency and cancer development.

Adult↗
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↗