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Biomedical subjects

M Macek

Publications and source records attributed to M Macek.

At least 19 recordsLinked to original sources
PubMed1992

Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.

The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15,000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the delta F508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.

Base Sequence↗
PubMed1991

[Determination of steroid hormones in the amniotic fluid in prenatal genetic diagnosis].

In amniotic fluid from the second trimester of pregnancy levels of total and free testosterone, 17 alpha-hydroxyprogesterone and dehydroepiandrosterone were assessed. The median levels of total testosterone during the 15th to 24th week are 0.82 +/- 0.31 nmol/l in pregnancies with male foetuses and 0.32 +/- 0.11 nmol/l in pregnancies with female foetuses. The levels of free testosterone assessed by calculation from concentrations of SHBG and total testosterone are 0.15 +/- 0.04 for male and 0.05 +/- 0.04 nmol/l for female foetuses. The diagnostic reliability of sex determination of the foetus from the total testosterone concentration in amniotic fluid is 94% and estimation of free testosterone increases it further. The median normal 17 alpha-hydroxyprogesterone levels during the 15th to 23rd week of pregnancy are 8.7 +/- 3.5 nmol/l and do not depend on the sex of the foetus and week of pregnancy. The levels of dehydroepiandrosterone in amniotic fluid from the second trimester of pregnancy are in male foetuses 0.64 +/- 0.33 nmol/l and 0.61 +/- 0.32 nmol/l in female foetuses and do not differ. Assessment of testosterone levels serves as a supplementary method for determination of the sex of the foetus and may play an important part in the prenatal diagnosis of syndromes with agenesis of testicles. Estimation of 17 alpha-hydroxyprogesterone is used in prenatal diagnosis of congenital adrenal hyperplasia, estimation of dehydroepiandrosterone can be used in the prenatal diagnosis of hereditary forms of adrenal hypofunction.

17-alpha-Hydroxyprogesterone↗
PubMed1991

Stable isotope dilution analysis of N-acetylaspartic acid in CSF, blood, urine and amniotic fluid: accurate postnatal diagnosis and the potential for prenatal diagnosis of Canavan disease.

A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-35.4 mumol/mmol creat.; in plasma 0.44 and 0.17-0.81 mumol/L; in cerebrospinal fluid 1.51 and 0.25-2.83 mumol/L; and in amniotic fluid 1.27 and 0.30-2.55 mumol/L. In a patient with Canavan disease, N-acetylaspartic acid concentration was elevated 80-fold in urine and 20-fold in plasma compared to the control means. A subsequent pregnancy of the mother was monitored and the N-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.

Amidohydrolases↗
PubMed1991

The direct early diagnosis of cystic fibrosis by the detection of the delta F508 CFTR gene mutation in a prematurely delivered boy.

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.

Chromosome Deletion↗
PubMed1990

[Strategies in prenatal diagnosis of cystic fibrosis after the introduction of DNA analysis. Initial experience].

The authors describe their experience with the prenatal genetic diagnosis of cystic fibrosis (CF), using DNA analysis in the first trimester of pregnancy in three families with a 25% risk of CF. The authors examined polymorphisms of probes J3.11, met D, met H, KM-19 and XV-2c. All families were fully informative when one or two probes were used. In two families the development of unaffected children--carriers of the gene for CF was proved. In one of these foetuses in the 17th and 21st week false pathological values of microvilillous enzymes were assessed. With regard to this possibility the authors do not recommend to supplement the DNA analysis in the first trimester by biochemical examination of amniotic fluid. The results were confirmed by delivery of unaffected children. In one family DNA analysis revealed the development of an unaffected homozygote, the pregnancy was, however, terminated by a miscarriage. In women with an increased risk of abortion the authors recommend therefore to make the molecular genetic examination during the second trimester from amniotic fluid cells.

Chorionic Villi Sampling↗
PubMed1990

[Experience with rapid molecular genetic diagnosis using the polymerase chain reaction].

The authors give an account of their experience with 1000 amplifications of DNA by the polymerase chain reaction for the prenatal diagnosis of cystic fibrosis. The method is demonstrated on examples of examinations of the informativity value and prenatal diagnosis in the first trimester of pregnancy in families with a 25% risk of cystic fibrosis, using J 3.11 (Msp I), met H (Msp I), KM 19 (Pst I), CS 7 (Hha I), Mp6d9 (Msp I), XV 2c (Taq I) probes. The authors summarize methodical check-up and safety measures to ensure the reliability of diagnoses made by the PCR method.

Cystic Fibrosis↗
PubMed1990

Beta-mannosidase deficiency: heterogeneous manifestation in the first female patient and her brother.

beta-Mannosidase deficiency was demonstrated in fibroblasts of a girl who showed severe psychomotor retardation, bone deformities and gargoylism and recurrent skin and respiratory infections and who died at 20 years of age from bronchopneumonia. This first demonstration of a female patient confirms the autosomal recessive inheritance of beta-mannosidosis. Further investigation of this gypsy family revealed beta-mannosidosis in an older brother with a milder manifestation of gargoyl facial dysmorphology, mental retardation, hearing impairment and recurrent infections. beta-Mannosidase activity was completely deficient in his cultured skin fibroblasts, leukocytes and plasma. In urine a characteristic disaccharide was present. Heterozygote levels of beta-mannosidase were found in fibroblasts and/or plasma of the parents and one sister.

Adolescent↗
PubMed1990

Frequency of the delta F508 mutation and flanking marker haplotypes at the CF locus from 167 Czech families.

This study analyses distribution patterns of the delta F508 mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and the cystic fibrosis (CF)-linked marker loci MET, D7S23, D7S399, and D7S8 in a sample of 167 (116 complete) CF families from Bohemia and Moravia (Czechoslovakia). DNA typing was performed by polymerase chain reaction amplification, restriction analysis, and agarose or polyacrylamide gel electrophoresis. The frequency of the delta F508 mutation in this sample is 67% and the frequency of the B haplotype is 77.6% on CF chromosomes. Linkage disequilibrium was found between delta F508 and all markers tested.

Chromosome Deletion↗
PubMed1990

Distribution patterns of the delta F508 mutation in the CFTR gene of CF-linked marker haplotypes in the German population.

We have measured the frequency of the delta F508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its association with cystic fibrosis (CF)-linked marker haplotypes in the German population. Based on the analysis of 400 CF chromosomes, the frequency of the delta F508 mutation is estimated to be 77.3%, the vast majority being associated with marker haplotype KM19-XV2c 2 1. Our data further suggest the presence of another frequent CF mutation associated with this marker haplotype.

Cystic Fibrosis↗
PubMed1990

The rapid molecular genetic diagnosis of cystic fibrosis by polymerase chain reaction: an experience report.

The authors report their experience with about two thousand DNA amplifications by polymerase chain reaction (PCR) in prenatal diagnosis of cystic fibrosis. The method is demonstrated on examples of diagnostic informativity and prenatal diagnosis examination in a family at 1 in 4 risk of the disease using closely CF-linked diagnostic polymorphisms: J3.11/MspI, MetH/MspI, CS7/HhaI, KM19/PstI, Mp6-d9/MspI and XV2c/TaqI, PCR methodology and safety precautions are discussed.

Cystic Fibrosis↗
PubMed1990

Cystic fibrosis marker testing in Bohemia with polymerase chain reaction.

Conditions for assessing KM-19 probe detected by Pst-1 restriction fragment length polymorphism (RFLP) by means of polymerase chain reaction were provided. Computer controlled mechanical arm with waterbaths and cloned heat-stable DNA polymerase was used. Results of KM-19 allelic frequencies on 90 cystic fibrosis chromosomes are presented. Allele two frequency was -0.833.

Alleles↗
PubMed1990

The experience with the foetal diagnosis of the cystic fibrosis in the second and first trimester.

The amniotic fluid activity of gamma glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP) and alcaline phosphatase (AP) and disacharidases was examined in 66 pregnancies with the risk of cystic fibrosis (CF) in the 17th-21st weeks of gestation. So far 28 pregnancies continue. The prenatal diagnosis was confirmed in all so far delivered children or aborted foetuses if the GGT activity was higher than 400 U/1 (10th percentile) or lower than 190 U/1 (3rd percentile) in the 17th-18th weeks. The results of other microvillar and ultrasound examinations were consistent with it. From 3 pregnancies with GGT activity in the range of 3-5 percentiles and abnormal activities of other microvillar enzymes, the CF was confirmed only in one aborted foetus with meconium ileus and with abnormal ultrasound examination. In other 2 pregnancies with normal ultrasound, healthy children were delivered. In 3 pregnancies with the GGT in the range of 5-10 percentiles and abnormal other microvillar enzymes, one false negative GGT and ultrasound examination was disclosed. The other 2 aborted foetuses did not exhibit the signs of CF in necropsy examinations. The meconium ileus was found in 2/4 of aborted foetuses with GGT lower than 3 percentiles, abnormal activities of other microvillar enzymes and abnormal ultrasound examination. The ultrasound examination was correct in 2/10 of pregnancies with GGT lower than 3 percentiles or abnormal activities of other microvillar enzymes. The GGT examination in 19th-21st weeks provided similarly reliable diagnostic results. The importance of fetal karyotyping and ultrasound elimination of other severe congenital anomalies is pointed out for critical interpretation of microvillar enzyme activities testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic Fibrosis↗