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M Kohoutová

Publications and source records attributed to M Kohoutová.

At least 19 recordsLinked to original sources
PubMed2006

[Mutations in tumor suppressor gene NBS1 in adult patients with malignancies].

BACKGROUND: Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS I are found in 1% Slavic populations. Increased occurrence of cancer was repeatedly reported in adult relatives of patients with Nijmegen breakage syndrome. Among children with oncological problematic, nonsignificantly increased frequency of NBS1 heterozygotes was found, which seems not to play any important role in cancerogenesis in childhood. However, the proportion of NBS heterozygotes among adult patients with malignancies could be significant and their therapy and follow up should respect their hyperradiosensitivity. METHODS AND RESULTS: Mutations in exon were studied in 706 adult patients with malignancies. We found 5 NBS heterozygotes, which not more than the population prevalence (1:129-165). Increased frequency of NBS heterozygotes was found among patients with colon and rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98). CONCLUSIONS: Surprisingly only one NBS heterozygote was found among 228 patients with nonHodgkin lymphoma, the malignancy which is a common complication in NBS homozygotes. Other types of malignancies were uncommon and only one R215W heterozygote was found. Comparison frequency of NBS heterozygotes with incidence NBS among person older than 70 years shows significant difference. Prevention of malignancies by avoidance from ionisation could be realized also in relatives of patients after identification of their genotype.

Adult↗
PubMed2006

[Hereditary forms of colorectal adenomatous polyposis].

BACKGROUND: Hereditary colorectal adenomatous polyposis syndromes are a predisposition to colorectal carcinoma development. The familial adenomatous polyposis is the most common analyzed syndrome that results from germline mutations in the APC gene. In addition to, the autosomal recessive form of polyposis has been recently reported. This disease is caused by germ-line mutations in the base excision repair MYH gene. The goal of this study is the identification of genetic causes of the colorectal polyposis, the determination of the frequency and type of the APC and MYH germ-line mutations in the set of families with colorectal polyposis in Czech population. METHODS AND RESULTS: The set of 103 probands with FAP was screened for germ-line APC mutations using the Protein Truncation Test and Denaturing Gradient Gel Electrophoresis. The MYH mutational screening was performed on 60 unrelated patients without detected APC mutations using the Denaturing High Performance Liquid Chromatography. Automated sequencing was carried out to identify found mutations. Totally, the 51 germ-line APC mutations (69,9%) are reported in the set of 72 probands including 31 novel mutations unique for Czech population. Molecular genetic analysis of the MYH gene revealed 15 DNA variations (25 %) including two patients identified as p.Y 165C/p.G382D compound heterozygotes (3,3%) and 13 polymorphisms or intronic changes (21,7%). The novel variants were detected in the 5 patients. CONCLUSION: Present study reflects the extremely heterogenous spectrum of the APC mutations in Czech population and confirms the previously reported data. However, the changes found in the MYH gene still need more extensive studies. Our results are important for genetic counselling and further clinical management among at-risk family members. It also enables distinction among different types of the colorectal polyposis.

Adenomatous Polyposis Coli↗
PubMed2004

Molecular analysis of the APC and MYH genes in Czech families affected by FAP or multiple adenomas: 13 novel mutations.

Familial adenomatous polyposis (FAP) is an autosomal dominant predisposition to colorectal cancer and is caused by germline mutations in the adenomatous polyposis coli gene. The most prominent clinical manifestation is the presence of hundreds to thousands of colorectal polyps. A milder phenotype is found in patients affected with AFAP/ multiple adenomas. We screened the entire APC coding region using the combination of DGGE, PTT and direct sequencing and identified causative mutations in 52 of 77 patients. Thirteen of the mutations found were novel. In addition, we also tested 21 APC mutation/negative probands for the two most common mutations in the MYH gene. Four patients showed neither dominant transmission of the disease nor evidence of APC mutations. In one of them the most common biallelic germline mutation in the MYH gene was detected. Correlations between the localization of germline mutations and clinical manifestations of the diseases are discussed.

Adenoma↗
PubMed2004

The influence of G-protein beta3-subunit gene and endothelial nitric oxide synthase gene in exon 7 polymorphisms on progression of autosomal dominant polycystic kidney disease.

BACKGROUND: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. We examined the influence of G-protein beta3-subunit C825T polymorphism and endothelial nitric oxide synthase Glu298Asp polymorphism on the progression of ADPKD towards end stage renal failure (ESRF). METHODS: 306 ADPKD patients (pts) were analyzed; 261 pts (136 males, 125 females) with ESRF, with subgroup of 73 pts (44 males, 29 females) with ESRF before 45 years (rapid progressors), 46 pts (20 males, 26 females) with ESRF later than in 63 years (slow progressors) and 45 ADPKD pts (17 males, 28 females) in mean age 51 years with serum creatinine under 110 micromol/L (slow progressors) and 100 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for G-protein beta3-subunit C825T genotype in exon 10 and for endothelial nitric oxide synthase Glu298Asp genotype in exon 7. RESULTS: The G-protein beta3-subunit C825T genotype exhibited no significant differences among the groups of slow progressors (6.6% (6/91) TT, 54.9% (50/91) CT, 38.8% (35/91) CC), rapid progressors (9.6% (7/73) TT, 46.6% (34/73) CT, 43.8% (32/73) CC), ADPKD group with ESRF between 40-63 years (9.2% (13/142) TT, 50% (71/142) CT, 40.8% (58/142) CC) and control group (12% TT, 44% CT, 44% CC). When comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages: males TT--51.7+/-8.8 years, CT--51.9+/-10.3 years, CC--49.7+/-10.2 years and females TT--56+/-9.9 years, CT--53.2+/-8.5 years, CC--53.9+/-8.7 years. The endothelial nitric oxide synthase Glu298Asp and Asp29Asp genotypes were significantly more frequent in rapid progressors (9.6% (7/73) Asp/Asp, 39.7% (29/73) Asp/Glu, 50.7% (37/73) Glu/Glu) and in ADPKD group with ESRF between 40-63 years (11.3% (16/142) Asp/Asp, 41.5% (59/142) Asp/Glu, 47.2% (67/142) Glu/Glu) in comparison with slow progressors (8.8% (8/91) Asp/Asp, 24.2% (22/91) Asp/Glu, 67.0% (61/91) Glu/Glu) and with control group (8% Asp/Asp, 32% Asp/Glu, 60% Glu/Glu) (Chi-square test, p<0.05). Comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages in males with Asp/Asp--54.9+/-10.4 years, Asp/Glu--50.2+/-9.4 years, Glu/Glu--51.0+/-10.4 years. We found out in homozygous Asp/Asp females significantly earlier onset of ESRF (49.2+/-5.6 years) in comparison with heterozygous females (53.3+/-7.2 years) and with Glu/Glu homozygous females (54.8+/-9.7 years) (t-test, p<0.05). CONCLUSION: We excluded the significance of G-protein beta3-subunit C825T polymorphism on the progression of ADPKD. We established the negative prognostic value of the carriers of Asp variant of eNOS polymorphism. Finding of new modifiers could have in future clinical consequences for ADPKD patients.

Adult↗
PubMed2002

Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease caused by mutations in at least three different loci. Mutations in the PKD2 gene are responsible for approximately 15% of the cases of the disease. We have screened 14 Czech families for mutation in the PKD2 gene. Clear evidence against linkage to the PKD1 gene was established by CA-repeat markers in five families. The disease could be linked to both genes according to linkage analysis in nine families but we have chosen these families because of the mild clinical course. An affected member from each family was analyzed by heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) for all 15 coding regions. Samples exhibiting shifted bands on HA or SSCP gels were sequenced. We detected five mutations (four new, and one which was previously described) and two polymorphisms. The four new mutations include one insertion, one deletion, one substitution (leading to premature translation stop), one amino acid substitution. Our results confirm that different point or small changes distributed throughout the PKD2 gene without clustering are responsible for the disease.

Codon, Nonsense↗
PubMed1999

[Perspectives in gene therapy of polycystic kidney disease].

An overview concerning principles and development of gene therapy from experimental models to first trials of application gene therapy in clinical medicine is provided. Increased attention is focused on specific methods of gene transfer into kidneys. Renal hereditary diseases represent an important subgroup of the diseases of the kidney, leading non rarely to chronic renal failure; (autosomal dominant) polycystic kidney disease remains to be one of the most frequent and clinically important. Preliminary conditions, including technical tools and pathophysiological insights to be fulfilled, as prerequisites for an application of gene therapy in polycystic kidney disease, are discussed.

Gene Transfer Techniques↗
PubMed1996

Major histocompatibility complex in the rat and blood pressure regulation.

The objective of this study was to evaluate whether the major histocompatibility complex of the rat can be related to blood pressure (BP) level and BP response to stress. Blood pressure was determined under light ether anesthesia or during moderate restraint stress in normotensive Lewis rats, in rat strains congenic with respect to their RT1 haplotype [LEW.1A (RT1a) and LEW.1W (RT1u)], and in their recombinant lines LEW.1AR1 (RT1ar1), LEW.1AR2 (RT1ar2), LEW.1WR1 (RT1wr1), and LEW.1WR2 (RT1wr2). Under light ether anesthesia, systolic blood pressure was similar in Lewis, LEW.1A, and LEW.1W rats. There were also no significant differences in blood pressure in LEW.1AR1 and LEW.1AR2 animals when compared with Lewis or LEW.1A rats. In contrast, BP was significantly increased in LEW.1WR2 rats. On the other hand, moderate restraint stress induced a BP increase in animals of all recombinant lines compared to the respective congenic strains. These results confirmed our previous finding in recombinant inbred strains about the significant role of RT1 complex in BP regulation. Moreover, our data indicated that BP can be influenced by interaction of individual regions of the RT1 complex on the genetic background of Lewis strain.

Anesthesia, Inhalation↗
PubMed1995

[Rheumatoid pericarditis: correlation with immunologic parameters].

In 35 patients with rheumatoid pericarditis the laboratory findings were compared with those of a group of 65 patients with rheumatoid arthritis without a pericardial exudate. The authors assessed the red cell sedimentation rate and serum levels of immunoglobulins G, M, A, semiquantitative values of the rheumatoid factor, circulating immunocomplexes, C3 and C4 complement components, the positivity of antinuclear antibodies and values of C-reactive protein. The authors found significantly elevated values of immunoglobulins M in patients with rheumatoid arthritis without a pericardial exudate. As regards the other investigated parameters the two compared groups did not differ.

Adult↗
PubMed1994

[Human gene therapy].

Human gene therapy is one of the promising approaches in treatment of genetic diseases and rapid development of molecular genetic methods is bringing this therapy in life. The article summarises the information about possibilities of this therapy, methods of gene transfer, first clinical experience and certain ethical aspects of this therapy.

Genetic Therapy↗