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Biomedical subjects

B Zoll

Publications and source records attributed to B Zoll.

At least 37 records · Page 2Linked to original sources
PubMed1994

Molecular and genetic characterisation of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families.

Eighteen German families with a history of paramyotonia congenita (PC) were characterised by genetic and mutational analysis at the SCN4A locus, which encodes the alpha-subunit of the adult skeletal muscle sodium channel. We concentrated our analysis primarily on these families to test the hypothesis that a predominance of one common mutation occurs in all German PC families and that this mutation arose in a common ancestor originating in the North-West of the country. The present eighteen PC families exhibit two different mutations (R1448C and R1448H) on various SCN4A dinucleotide repeat haplotypes and therefore the majority of the mutations probably occurred independently. However, the R1448H mutation is extremely frequent in the North-West of Germany (Ravensberger Land) on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. Our results suggest that the R1448C/R1448H mutations are by far the most common to be associated with the PC phenotype in the German population.

Base Sequence↗
PubMed1994

Prevalence of beta allele of the insulin gene in type II diabetes mellitus.

Fifty-two patients and 36 controls were compared in a search for insulin gene variants among type II diabetic patients with fasting hyperinsulinemia (above 90 microU/ml) and a fasting C-peptide to insulin molar ratio between 1.11 and 1.50. Alpha and beta alleles of the insulin gene were characterized by restriction analysis of polymerase chain reaction (PCR) products and direct sequencing. The more frequent occurrence of the alpha allele of the insulin gene within the control population as compared with a prevalence of the beta allele in the diabetic patients (P, 0.05) was observed. The beta allele, usually described as the rare allele, seems to be associated with the disease.

Adult↗
PubMed1994

Interstitial deletion of 22q11 in DiGeorge syndrome detected by high resolution and molecular analysis.

Two patients with DiGeorge syndrome (DGS), one with and one without characteristic dysmorphic facial features, were studied by high resolution banding, fluorescence in situ hybridization (FISH) and quantitative Southern blotting. In both patients, even in the one with no typical facial stigmata, a microdeletion within 22q11.2 was detected. FISH analysis, in particular, is most useful in screening for 22q11.2 segmental monosomy in patients with DGS and DGS-related features.

Blotting, Southern↗
PubMed1994

Hereditary pancreatitis--a case report.

A female patient with hereditary chronic pancreatitis is described. She presented initially at the age of 18 years with abdominal pain due to acute pancreatitis. Predisposing etiological factors were not recognized. During the ensuing years she had recurrent episodes of abdominal pain and chronic pancreatitis with extensive pancreatic calcifications was finally demonstrated. Six other family members within three generations were affected by chronic pancreatitis suggesting an autosomal dominant mode of transmission. None of the affected patients showed signs of diabetes mellitus, aminoaciduria or hyperparathyroidism.

Adult↗
PubMed1993

Recurrent mutations in the factor IX gene: founder effect or repeat de novo events. Investigation of the German haemophilia B population and review of de novo mutations.

The investigation of 114 unrelated patients, representing about half the sample of the German haemophilia B population, enabled us to delineate the causative mutation in 103 (90.4%) haemophilic factor IX genes. Of these 103 cases 84 (81.6%) turned out to be unique molecular events, the remainder being repeats. Haplotype analysis revealed that the great majority, if not all, of these recurrent observations occurred independently. This conclusion is supported by our finding that three de novo mutations could be demonstrated at two sites of frequent mutation. A further 20 de novo events could be established in an unselected sample of 37 families with sporadic haemophilia B and 37 families with a history of the disease. Altogether, the germ line of origin could be determined in 21 of these 23 cases, thereby indicating a ratio of male to female mutation rates close to 2. On the basis of the data available, it is becoming clear that rearrangements in the factor IX gene (35.4% of de novo cases) are responsible for haemophilia B at a higher frequency than has been observed today (12.3%). More than two-thirds of the de novo cases cause the severe form of the disease, thereby reflecting the deficit of these haemophilic genes in the actual gene pool because of excess mortality in the past. In addition 40% (12/30) of the de novo single-base mutations were transitions at CpG dinucleotides. Compared with the expected at-random frequency, this observation indicates an 83-fold enhancement of mutation at CpG.

DNA Mutational Analysis↗
PubMed1993

Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients.

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.

Biomarkers, Tumor↗
PubMed1993

Prenatal diagnosis of congenital nephrosis of the Finnish type (CNF) in the second trimester.

Congenital nephrosis of the Finnish type is an hereditary, autosomal recessive disease which leads to death in early infancy. This is a case report concerning an affected fetus with legal interruption in the 24th week of gestation on the basis of certain sonographic changes in the fetal kidneys and changes in the protein profile in amniotic fluid, which were consistent with nephrotic damage of the kidneys. Light and electron microscopy showed evidence of CNF, i.e. increase of mesangial matrix and cells in glomeruli, dilated tubular segments, and effaced and plumb foot-processes of the glomerular epithelial cells. Antenatal diagnosis of CNF therefore seems feasible in the second trimester of gestation by means of AFP determinations in maternal serum and amniotic fluid as well as by using sonographic criteria and determination of proteins in amniotic fluid.

Amniotic Fluid↗
PubMed1993

Trisomy 13 (Patau syndrome) with an 11-year survival.

Trisomy 13 is very rare in live-born children. Only a small number of these children survive the first year and very few cases are reported to live longer. Survival time depends partly on the cytogenetic findings--full trisomy 13 or trisomy 13 mosaicism--and partly on the existence of serious somatic malformations. We report on a 11-year-old girl with full trisomy 13. In this case, missing cerebral and cardiovascular malformations probably allowed the long survival.

Abnormalities, Multiple↗
PubMed1993

A case of full triploidy (69,XXX) of paternal origin with unusually long survival time.

Triploidy is a rare disorder in live-born children and these infants generally die within the first hours after birth. We report here on a girl with full triploidy and multiple malformations, who survived for 10 1/2 weeks. The extra set of haploid chromosomes was of paternal origin, as shown by chromosomal banding techniques.

Abnormalities, Multiple↗
PubMed1993

Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).

Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal muscles with marked hypertrophy in the legs. A transient muscle weakness is particularly pronounced in the arms and hands and is a typical symptom of the disorder. Recently, we showed complete linkage of the disorder GM to the gene (CLCN1) coding for the skeletal muscle chloride channel CLC-1 and the TCRB gene on chromosome 7 in German families. In the study presented here we performed linkage analysis on 14 new GM families. The GM locus was again completely linked to both the CLCN1 and the TCRB gene in all families with a combined lod score of Z = 9.26 at a recombination fraction of theta = 0.00. This confirms our previous data and supports the hypothesis that GM is a genetically homogeneous disorder. The previously detected T to G missense mutation is found on 15% of the 66 GM chromosomes counted so far.

Alleles↗
PubMed1993

Direct versus indirect molecular diagnosis of fragile X mental retardation in 40 German families at risk.

In order to test whether the direct molecular diagnostic approach for fragile X mental retardation (Martin-Bell syndrome, MBS) really makes diagnosis of this disease more precise, we evaluated the results of direct diagnosis in 40 German families at risk together with the results of an earlier study with closely linked flanking markers in the same families. Of 84 men analysed, 43 showed clinical signs. In 39 of these affected men the disease could be confirmed by direct diagnosis. Compared to cytogenetic data, one man was false negative and two were false positive. Two men, whose status could not be determined by means of RFLP data, proved to be normal transmitting males (NTMs). However, the possibility of being an NTM had to be rejected in one case on RFLP data. Fragile X syndrome could be confirmed in 10 of the 13 women with clinical signs. Compared to cytogenetic data there were three cases of false negative results and one of false positive. All 36 obligate carrier women were detected by the direct approach. In addition, 22 women were newly identified as normal transmitting females (NTFs), among them one woman who could not be identified by cytogenetic means or by analysis with closely linked markers. These findings are discussed in view of the relative reliability of the three diagnostic approaches to MBS. Special attention is drawn to the significance of false negative and false positive results in direct diagnosis.

Base Sequence↗
PubMed1992

The skeletal muscle chloride channel in dominant and recessive human myotonia.

Autosomal recessive generalized myotonia (Becker's disease) (GM) and autosomal dominant myotonia congenita (Thomsen's disease) (MC) are characterized by skeletal muscle stiffness that is a result of muscle membrane hyperexcitability. For both diseases, alterations in muscle chloride or sodium currents or both have been observed. A complementary DNA for a human skeletal muscle chloride channel (CLC-1) was cloned, physically localized on chromosome 7, and linked to the T cell receptor beta (TCRB) locus. Tight linkage of these two loci to GM and MC was found in German families. An unusual restriction site in the CLC-1 locus in two GM families identified a mutation associated with that disease, a phenylalanine-to-cysteine substitution in putative transmembrane domain D8. This suggests that different mutations in CLC-1 may cause dominant or recessive myotonia.

Amino Acid Sequence↗
PubMed1992

Prenatal diagnosis of the Pallister-Killian mosaic aneuploidy syndrome by CVS.

Prenatal cytogenetic analysis at 11 weeks of gestation revealed an abnormal karyotype 47,XX,+mar in all metaphases obtained from a chorionic villi sample after 24 h culture. Karyotyping of amniotic fluid cells in the second trimester showed mosaicism 47,XX,+i(12p)/46,XX with 10% aneuploid cells. The pregnancy was terminated at 20 weeks of gestation on the patient's request. The aborted fetus showed typical manifestations of the Pallister-Killian mosaic aneuploidy syndrome. The identity of the supernumerary isochromosome 12p was proven by LDH isozyme electrophoresis using cultured fibroblasts and by nonradioactive in situ hybridization using a biotinylated set of chromosome 12-specific DNA probes.

Abnormalities, Multiple↗
PubMed1992

Amplification and expression of the epidermal growth factor receptor gene during the progression of neuroepithelial tumours in vivo.

The epidermal growth factor receptor (EGFR) gene is homologous to the oncogene c-erbB. The occurrence of amplification and rearrangements at the EGFR gene locus is associated with malignancy in neuroepithelial tumours. Sixteen neuroepithelial tumours from eight patients with recurrence of their neoplasms were analysed for changes at the EGFR gene locus and for expression of EGFR. Ten tumours from five patients lacked changes at the EGFR gene locus. Three of eight individuals showed EGFR gene amplifications in both tumours with a higher grade of amplification in the second tumour. In addition to amplification, a rearrangement was found in both tumours of the first patient. In the second case an amplification of chromosome-7-specific c-met sequences was found in the regrown tumour, suggesting that a polysomy 7 was at least partly responsible for the higher copy number of the EGFR sequences. In both tumours of the third patient with EGFR gene amplification different alleles were amplified. In contrast to the findings at the DNA level the EGFR expression, analysed by immunohistochemical techniques, showed a more heterogeneous pattern after tumour progression.

Adult↗
PubMed1992

Alterations of the c-erbB2 gene in human breast cancer.

DNA amplification, RNA overexpression and p185 protein expression of the c-erbB2 oncogene were investigated in 109 cases of breast cancer with the aim of evaluating any correlation between the different methods. A correlation between Southern blotting and immunohistochemical analysis of paraffin-embedded material was found. Thus, amplification of the c-erbB2 oncogene leads to overexpression of the p185 protein. By contrast, no statistical correlation could be shown between RNA overexpression, measured by Northern blotting, and immunohistochemical p185 membrane stainings. It is of special interest that most of the cases that are positive for Northern blotting and negative for immunochemistry are negative for Southern blotting as well. Contradictory findings between RNA overexpression and lack of immunohistochemical staining of p185 give rise to the assumption that a defective protein is encoded, which cannot be incorporated into the substructures of the tumour cell membrane. When screening for point mutations in the transmembrane domain of the c-erbB2 oncogene, no point mutation could be detected, either by using the endonuclease FokI, which cuts at position 2012 (the point mutation in the neu gene of the rat), or by direct sequencing.

Base Sequence↗
PubMed1992

[Discovery of the gene makes the direct molecular genetic diagnosis of Martin-Bell syndrome possible].

UNLABELLED: FORMULATION OF QUESTION: In 1991 four independent groups of geneticists succeeded in replacing the comparatively unreliable cytogenetic and indirect molecular diagnostics of the X-linked Martin-Bell-syndrome (MBS) by a more accurate approach. METHODS AND RESULTS: Fine structure analysis of the disease locus at Xq 27.3 led to the discovery of the fragile X mental retardation gene I (FMR I-gene), the mutative changes of which are responsible for the disease and can easily be detected in Southern hybridizations with gene probes out of this area. The observed changes are strong amplification of a repetitive CGG-motive in exon I of the gene in patients, a more moderate one in symptom-free carriers of the disease and changes in the promotor region of the gene to a varying extent in patients and carriers. CONCLUSION: This direct molecular diagnosis of MBS enables a safe identification of patients and carriers of the disease. A combined analysis of the observed mutations makes possible prenatal diagnosis, discriminating between carriers with and without symptoms. Especially this is necessary, since 20% of male and 50 to 70% of female mutation carriers are phenotypically normal.

Child↗
PubMed1992

[Martin-Bell syndrome. Improved possibilities for molecular genetic diagnosis].

In a former molecular segregation analysis of fra x mental retardation in 27 families at risk we had used marker gene probes with a relatively high recombination fraction. Thus, the resulting risk for a false diagnosis was comparatively high. To diminish this risk, all families were reanalyzed with the newly invented and more closely linked gene probes RN1A, VK23B, VK21C and U6.2. Using these probes as molecular markers we performed Southern hybridization experiments. The remaining diagnostic risk due to recombination events could be reduced to 2% up to 20% compared to preanalysis. The portion of informative families (91%) is in good agreement with the expected cumulative heterozygosis frequency of 93.4% for all 4 markers investigated. This high frequency and the very low remaining risk for a false diagnosis therefore enable a far more precise molecular diagnostic of the Martin-Bell-syndrome.

Abnormalities, Multiple↗