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Biomedical subjects

A Gal

Publications and source records attributed to A Gal.

At least 145 records · Page 8Linked to original sources
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

Retraumatization of Holocaust survivors during the Gulf War and SCUD missile attacks on Israel.

The purpose of this work was to study the reaction to a new threat and a new trauma of people severely traumatized in the past, when the new trauma had associations with the original one caused by the Holocaust. The situation created during the Gulf War gave a rare occasion to study it. We also wanted to check if the reaction of Holocaust survivors to the war differed from that of the general population. In addition we wanted to find out if there was a difference in reaction to the war between two clinical populations: Holocaust survivors and patients who are not Holocaust survivors. Sixty-six Holocaust survivors living in Israel, 31 of them undergoing psychiatric or psychological treatment either as in-patients or as out-patients, were interviewed during the Persian Gulf War. In addition to the clinical group, there was a non-clinical group of 35 Holocaust survivors--21 whose homes were not damaged by SCUD missiles, and 14 whose homes were damaged by missiles. Those whose homes were damaged by SCUD missiles were retraumatized, and showed reactivation or exacerbation of the survivor syndrome. Six of them displayed the full syndrome of PTSD.

Aged↗
PubMed1994

Thr4Lys rhodopsin mutation is associated with autosomal dominant retinitis pigmentosa of the cone-rod type in a small Dutch family.

A mother and daughter with autosomal dominant retinitis pigmentosa (adRP) were found to carry a cytosine-to-adenine transversion mutation at codon 4 of the rhodopsin gene. This mutation predicts a substitution of lysine for threonine at one of the glycosylation sites in the rhodopsin molecule (Thr4Lys). Both patients presented with a similar phenotype including a tigroid pattern of the posterior pole and a regional predilection for degenerative pigmentary changes in the inferior retina with corresponding visual field defects. The electroretinographic pattern was suggestive of RP of the cone-rod type. This report documents the clinical findings associated with this defined mutation of the rhodopsin gene.

Adult↗
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 in patients with mucopolysaccharidosis type II suggests that DXS466 maps within the Hunter gene.

Hunter disease is an X-linked mucopolysaccharidosis caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). Using the IDS cDNA and DNA probes corresponding to loci flanking the IDS locus, we performed molecular genetic studies in two patients with Hunter syndrome. An interstitial deletion spanning the middle part of the IDS gene was found in the first patient. The second patient carries a gross gene rearrangement that can be detected after HindIII or EcoRI digestion of genomic DNA, and is similar to that found recently in seven unrelated Hunter patients. Our data suggest that the structural aberration observed is a partial intragenic inversion. As the same altered hybridization pattern is also revealed by the recently described anonymous DNA probe II-10, which recognizes a frequent TaqI restriction fragment length polymorphism at the DXS466 locus, we conclude that DXS466 maps within the IDS gene, probably in an intron.

Blotting, Southern↗
PubMed1993

Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome).

Mutations of the iduronate-2-sulfatase gene were identified in 16 patients with mucopolysaccharidosis type II (Hunter syndrome). Together with another 10 cases reported by us earlier it emerges that about 20% of the patients have deletions of the whole gene or other major structural alterations. One, two or three base pair deletions are found in about 23% of the cases while the remaining about 57% carry point mutations predicting amino acid replacement, premature termination of translation, or aberrant splicing. Molecular analysis of mRNA in splice site mutants showed that these latter defects frequently resulted in use of cryptic splice sites in exons or introns. 62% of the small deletions and point mutations have occurred in 3 of the 9 iduronate-2-sulfatase gene exons. Knowledge of the primary genetic defect allows fast and reliable carrier detection and prenatal diagnosis as well as insight into the relationship between genotype and phenotype.

Amino Acid Sequence↗
PubMed1993

Exclusion of the involvement of all known retinitis pigmentosa loci in the disease present in a family of Irish origin provides evidence for a sixth autosomal dominant locus (RP8).

Retinitis Pigmentosa (RP) is the most prevalent degenerative retinal disease of mendelian origin, currently affecting approximately 1.5 million people worldwide. To date it has been established that a minimum of five different genes maybe involved in the pathogenesis of autosomal dominant forms of RP (adRP). The genes encoding two retinal specific proteins, rhodopsin and peripherin/RDS, have been implicated in causing adRP due to the observation of many different mutations in these genes in patients suffering from RP. The three remaining adRP genes have been mapped to specific regions of human chromosomes but as yet are uncharacterized. We have investigated if there is evidence for the presence of another locus in the genome which when mutated causes adRP. We have utilised polymorphic genetic markers which have previously been mapped to each of the regions known to harbour adRP genes, to test for the exclusion or linkage of the disease gene segregating in a pedigree of Irish origin and find no evidence for linkage. Hence we provide definitive evidence for the involvement of yet another locus. The implications of high levels of genetic heterogeneity inherent in adRP are discussed in relation to diagnosis, prognosis and future therapies.

Chromosome Mapping↗
PubMed1993

Modulation of glucocorticosteroid binding in human lymphoid, monocytoid and hepatoma cell lines by inflammatory cytokines interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha.

In order to elucidate the role of the inflammatory cytokines in regulating glucocorticosteroid binding (GCSB) and glucocorticosteroid receptor (GR) level we incubated a B-cell line (CESS), a promonocytic cell line (U937) and a hepatoma cell line (HepG2) in the presence of varying concentrations of IL-1 beta, IL-6 and TNF-alpha for 24 h. Glucocorticosteroid binding was determined by the method of 'whole cell uptake', and the cellular appearance of the glucocorticosteroid receptor was detected by immunocytochemistry. A rise in the glucocorticosteroid binding was induced by all three cytokines. The increase in level of glucocorticosteroid receptors in the cells shown by immunocytochemistry was much more pronounced. However, antagonistic effects were demonstrated by both methods between IL-6 and TNF-alpha, and between IL-1 beta and TNF-alpha when they were applied simultaneously, in U937. Present data suggest that local imbalance in the ratio of these three cytokines in different pathological cases might influence the glucocorticosteroid sensitivity of the lymphocytes, monocytes and hepatocytes as target cells.

Animals↗
PubMed1993

Multipoint linkage analysis in X-linked juvenile retinoschisis.

Thirteen families with X-linked juvenile retinoschisis (XLRS) were studied in order to evaluate the linkage relationship between the XLRS locus (RS) and seven X-chromosomal DNA markers. Linkage was found between RS and DXS9 (theta max = 0.11, Zmax = 4.17), DXS16 (theta max = 0.06, Zmax = 7.72), DXS41 (theta max = 0.06, Zmax = 8.13) and DXS43 (theta max = 0.03, Zmax = 6.11). Recombinants were found between RS and all loci studied. Multipoint linkage analysis and recombination analysis significantly favour the order of Xpter-(DXS9, (DXS16-DXS43))-RS-DXS41-Xcen.

Adult↗