Search PubMed⌕ Search

Biomedical subjects

E Schwinger

Publications and source records attributed to E Schwinger.

At least 91 records · Page 5Linked to original sources
PubMed1995

Frequency of common cystic fibrosis gene mutations in chronic bronchitis patients.

It has been suggested that the delta F508 deletion, the most common mutation in the cystic fibrosis (CF) gene, might be linked to chronic bronchial hypersecretion. We investigated whether such an association could be found in chronic bronchitis, since chronic bronchial hypersecretion is an important and specific element of chronic bronchitis. We screened 100 patients hospitalized for chronic bronchitis with six of the most frequently occurring CF gene mutations: delta F508, R553X, G542X, G551D, N1303K, and 621-1G-->T. Only one patient affected by chronic bronchitis and diffuse bronchiectasis was heterozygous for the deletion delta F508; no other mutations were found. This is not significantly different from the expected frequency of CF carriers in northern Europe, which is 1 in 25. Thus, no association between the most commonly occurring cystic fibrosis genes and chronic bronchitis is likely to exist and routine screening of patients without further signs of cystic fibrosis would seem to be of no benefit in northern Europe.

Aged↗
PubMed1995

Autosomal dominant exudative vitreoretinopathy: linkage analysis and its clinical application.

Close linkage without recombination (Zmax = 7.383 at Theta = 0.00) was found between the locus for autosomal dominant exudative vitreoretinopathy (Criswick-Schepens) and the locus D11S388 in 11q14.3-q21. We report on the application of data from linkage studies in the diagnostic management of this disease. To determine the disease risk for two newborn children of two affected mothers more precisely, indirect genotype analysis was performed by typing their DNA for three DNA polymorphisms, the loci of which have been shown to be closely linked to the locus of autosomal dominant exudative vitreoretinopathy.

Adult↗
PubMed1994

Mapping of the autosomal dominant exudative vitreoretinopathy locus (EVR1) by multipoint linkage analysis in four families.

Autosomal dominant exudative vitreoretinopathy is a disorder affecting primarily the development of the human retinal vascular system. The disease locus has recently been assigned to 11q13-q23 by linkage studies in two families. Two-point analysis on a total of four families has now revealed close linkage (Zmax = 8.34 at theta = 0.00) between the disease locus and D11S873. Multipoint linkage analysis mapped the disease locus between D11S527/D11S533 and D11S35 with a maximum lod score of over 11 directly at D11S873. No evidence appeared for genetic/linkage heterogeneity among the four families examined.

Chromosome Mapping↗
PubMed1994

Molecular characterization of the androgen receptor gene in boys with hypospadias.

Development of male external genitalia is dependent on androgens, and karyotypic males lacking appropriate levels of androgens or functionally normal receptors may show abnormal virilization. Mutations in the androgen receptor gene cause abnormal receptor function and diverse mutations may be associated with heterogeneous clinical signs of androgen insensitivity. In this study, we have searched for the existence of androgen receptor gene mutations carried by some patients with hypospadias. Genomic DNA samples from peripheral blood leucocytes from 21 patients with different degrees of hypospadias were studied. Analysis of the androgen receptor gene was performed by exon-specific amplification using polymerase chain reaction, single strand conformation polymorphism analysis, and direct genomic sequencing. Although a silent polymorphism was identified in exon 1 of the androgen receptor gene, the majority of patients studied (20/21) did not carry androgen receptor gene mutations. One patient with severe hypospadias and bilateral cryptorchidism was found to carry a point mutation in exon 8. We conclude that mutations in the androgen receptor gene may be carried by subset of patients with genital ambiguity presenting primarily with hypospadias, but this is not the underlying cause in the majority of cases. Characterization of this genetic defect may be important for classification and subsequent conservative therapeutic approaches for these patients.

Base Sequence↗
PubMed1994

Teratogenic effects in a case of maternal treatment for acute myelocytic leukaemia--neonatal and infantile course.

Experience with the use of cytotoxic drugs in the first trimester of pregnancy is limited. We report on the clinical phenotype and infantile development of a girl born to a 36-year-old mother. Before recognition of pregnancy, the latter had been treated for acute myelocytic leukaemia receiving cytarabine, daunorubicin and doxorubicin at conception and cytarabine and thioguanine at about 35-37 days post conception. At delivery, there were severe brachycephaly, hypoplasia of the anterior cranial base and the midface as well as synostoses of both coronal and metopic sutures. Further findings included bilateral four-finger hands with hypoplastic thumbs and absent radii. This phenotype is reminiscent of the Baller-Gerold syndrome. The child, at present 15 months old, has had to undergo two operations for fronto-orbital advancement because of insufficient growth of the mid-face, nasal airway hypoplasia and increased intracranial pressure. Motor milestones are slightly retarded--neurodevelopment is otherwise normal. These findings are discussed in the context of the few previous reports and are particularly important for future genetic counselling.

Abnormalities, Drug-Induced↗
PubMed1994

Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness.

The locus for autosomal dominant congenital stationary night blindness (adCSNB) has recently been assigned to distal chromosome 4p by linkage analysis in a large Danish family. Within the candidate gene encoding the beta-subunit of rod photoreceptor cGMP-specific phosphodiesterase (beta PDE), we have identified a heterozygous C to A transversion in exon 4, predicting a His258Asp change in the polypeptide. We found a perfect cosegregation (Zmax = 22.6 at theta = 0.00) of this mutation with the disease phenotype suggesting that this missense mutation is responsible for the disease in this pedigree. Homozygous nonsense mutations in the beta PDE gene have been found recently in patients with autosomal recessive retinitis pigmentosa, a common hereditary photoreceptor dystrophy.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Gene for autosomal dominant congenital stationary night blindness maps to the same region as the gene for the beta-subunit of the rod photoreceptor cGMP phosphodiesterase (PDEB) in chromosome 4p16.3.

We studied a large multigeneration Danish family with autosomal dominant congenital stationary night blindness. Both electrophysiological and psychophysical findings in affected family members were identical to those reported in patients from the 'Nougaret family'. The disease locus in the Danish family has now been mapped by demonstrating close linkage without recombination (Q = 0.00 at Zmax = 14.4) to the locus for alpha-L-iduronidase assigned to chromosome 4p16.3. Interestingly the gene for the beta-subunit of the rod photoreceptor cGMP-specific phosphodiesterase maps to the very same chromosomal region.

Chromosome Mapping↗
PubMed1994

Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.

A group of 46 European patients with mucopolysaccharidosis type I (MPS I) was screened for mutations of the alpha-L-iduronidase gene. The 2 common nonsense mutations, W402X and Q70X, were identified in, respectively, 37% and 35% of mutant alleles. Considerable differences were seen in the frequency of these 2 mutations in patients from North Europe (Norway and Finland) and other European countries (mainly The Netherlands and Germany). In Scandinavia, W402X and Q70X account for 17% and 62% of the MPS I alleles, respectively, while in other European countries W402X is about 2.5 times more frequent (48%) than Q70X (19%). Eight novel mutations are described including 4 missense mutations, 1 nonsense mutation, 1 insertion of 2 base pairs, and 2 deletions of 1 and 12 base pairs.

Alleles↗
PubMed1994

"Compensatory" uniparental disomy of chromosome 21 in two cases.

Two cases of growth failure, microcephaly, facial dysmorphism, muscular hypertonia, and severe psychomotor retardation are described. At birth, both cases had cytogenetic mosaicism in lymphocytes and skin fibroblasts, in case 1 ring chromosome 21 and monosomy 21 and in case 2, deletion of chromosome 21 and monosomy 21. At a later age the lymphocyte karyotype changed almost completely to 46,XX, but the fibroblast karyotype remained as before. DNA polymorphism analysis described elsewhere indicated that the 46,XX lymphocytes contained two identical chromosomes 21 (isodisomy), in case 1 inherited from the father and in case 2 from the mother. The isodisomy was the result of duplication of a chromosome in mitosis after the loss of the homologous abnormal chromosome ("compensatory isodisomy"). We report here that this cytogenetic mechanism can result in false normal cytogenetic findings. The phenotypes were attributed to the cells with monosomy 21 in case 1 and to the deletion and monosomy of chromosome 21 in case 2.

Adolescent↗
PubMed1994

Mulvihill-Smith syndrome: case report and review.

We report a 20 year old man with short stature, microcephaly, unusual facies, numerous pigmented naevi, hypodontia, immunodeficiency, and a high pitched voice. Tympner et al had assumed that the patient had a new syndrome of "progressive combined immunodeficiency and ectomesodermal dysplasia". We show here that the condition is identical to the Mulvihill-Smith syndrome (McKusick 176690), a progeroid disorder described in four or possibly five sporadic cases to date. We describe his clinical progress up to the age of 20 years. Our patient suffered from severe viral infections, allergic rhinitis and conjunctivitis, delayed puberty, visual loss, modest achievement in high school, and reactive depression. The immunological, facioskeletal, and dental abnormalities are presented in detail.

Abnormalities, Multiple↗
PubMed1993

Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate-2-sulphatase gene.

A number of mutations in the X-chromosomal human iduronate-2-sulphatase gene have now been identified as the primary genetic defect leading to the clinical condition known as Hunter syndrome or mucopolysaccharidosis type II. The mutations that are tabulated include different deletions, splice-site and point mutations. From the group of 319 patients thus far studied by Southern analysis, 14 have a full deletion of the gene and 48 have a partial deletion or other gross rearrangements. All patients with full deletions or gross rearrangements have severe clinical presentations. Twenty-nine different "small" mutations have so far been characterised in a total of 32 patients. These include 4 nonsense and 13 missense mutations, 7 different small deletions from 1 to 3 bp, with most leading to a frameshift and premature chain termination, and 5 different splice-site mutations also leading to small insertions or deletions in the mRNA. A 60 bp deletion, that results from a new donor splice-site, has been observed in five unrelated patients with relatively mild clinical phenotypes. This information will not only be useful for MPS II patient and carrier diagnosis, but also will aid in the understanding of the structure and function of iduronate-2-sulphatase, and possibly in correlating genotype with phenotype.

Gene Deletion↗
PubMed1993

Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa.

Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 (theta max = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20.

Australia↗
PubMed1993

Polyploidies in abortion material decrease with maternal age.

Among 639 spontaneous abortions between the 8th and 14th week of gestation 342 (53.5%) revealed an abnormal karyotype. While the rate of trisomies distinctly increased with advancing maternal age, a decrease in the rate of 45,X conceptuses and polyploidies was observed among abortions from older women. The overall relation of XXXX:XXYY among the tetraploidies was 14:11 and that of XXX:XXY:XYY among the triploidies was 26:36:1. However, when the latter was related to maternal age, a reversal of the XXX:XXY ratio of 1:2 in the younger to 2:1 in the older age groups became evident. Furthermore a decrease in the rate of "paternally" derived partial hydatidiform moles was found among the triploid abortion specimens from older women. From these observations we conclude that digyny plays a major role in the origin of triploidy in the increased maternal age groups, while diandry related to immaturity of oocytes and impairment of oocyte cortical function is more frequent in triploid abortions from younger women.

Abortion, Spontaneous↗