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Biomedical subjects

A Gal

Publications and source records attributed to A Gal.

At least 127 records · Page 7Linked to original sources
PubMed1995

Distribution of extracellular matrices, matrix receptors, and transforming growth factor-beta 1 in human and experimental lung granulomatous inflammation.

Aberrant deposition of extracellular matrices (ECMs) may affect lung inflammation by influencing cell adhesion, migration, and activation. Little is known about the expression of ECMs in lungs with granulomatous inflammation. Therefore the authors investigated the distribution of ECMs, matrix receptors of the integrin family, and transforming growth factor-beta 1 (TGF-beta 1) in lungs from patients with pulmonary sarcoidosis and animals with experimental granulomatosis. Immunohistochemistry revealed increased deposition of type I collagen and fibronectin in human lung granulomas when compared with healthy human lungs. Procollagen type I and cellular fibronectin also were increased, suggesting local synthesis of ECM in sarcoid granulomas. These findings were accompanied by increased staining for fibronectin (alpha 5 beta 1) and collagen (alpha 2 beta 1) integrin receptors. The matrix-inducing cytokine TGF-beta 1 was co-distributed with the aforementioned molecules in the granulomas, whereas no significant staining for TGF-beta 1 was found in healthy lungs. Similar to sarcoid lungs, analysis of lung sections obtained from a murine model of granuloma formation revealed increased expression of fibronectin, collagen, integrin receptors, and TGF-beta 1 within granulomas. Based on these observations, there is increased expression of ECM and matrix receptors in both human and experimental lung granulomas. Such alterations may influence the recruitment and activation of inflammatory cells and fibroblasts, promoting granuloma formation and remodeling of tissue by fibrosis. Activation of mononuclear cells resulting in production of TGF-beta 1 is likely to contribute to the changes described.

Animals↗
PubMed1995

Autosomal recessive retinitis pigmentosa locus maps on chromosome 1q in a large consanguineous family from Pakistan.

A large Pakistani family with several consanguineous marriages is described, in which autosomal recessive retinitis pigmentosa is segregating. Linkage studies revealed close linkage between the disease locus and six loci on chromosome 1q (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging from 0.988-4.657 at theta = 0.065-0.235. However, the analysis of individual nuclear families showed very close linkage without recombination in three branches and several recombinants and negative lod scores throughout in the fourth branch. These results strongly suggest that mutations of two different genes are responsible for the disease in the 'linked' and 'unlinked' branches. Parallel to the linkage heterogeneity, clear phenotypic differences have been observed among the 'linked' and 'unlinked' parts. Our findings demonstrate that in case of recessive disorders the possibility of non-allelic genetic heterogeneity should always be considered, even within the same kindred and in genetic isolates if a largely extended pedigree is analysed.

Chromosome Mapping↗
PubMed1995

Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS/peripherin gene.

Clinical phenotypes of patients with mutations in the human RDS/peripherin gene are described. A 67-year-old woman, who carried a 1 base pair deletion in codon 307, presented with typical late onset autosomal dominant retinitis pigmentosa (RP). In another autosomal dominant pedigree, a nonsense mutation at codon 46 caused 'inverse' retinitis pigmentosa-like fundus changes associated with progressive cone-rod degeneration in a 58-year-old man, whereas his 40-year-old son presented with yellow deposits in the retinal pigment epithelial layer resembling a pattern dystrophy, and with moderately reduced rod and cone function, as determined by two colour dark adapted threshold perimetry and electroretinography. It is suggested that both clinical pictures within this latter family may represent manifestations of fundus flavimaculatus. The clinical data of the three patients provide further evidence for the remarkable variety of disease expression within and between families with mutations in the RDS/peripherin gene. Currently, the most comprehensive statement could be that RDS/peripherin mutations are associated either with typical RP or with various forms of flecked retinal disease.

Adult↗
PubMed1995

Autosomal dominant retinitis pigmentosa locus on chromosome 19q in a Japanese family.

A large four generation Japanese family was studied, in which autosomal dominant retinitis pigmentosa (ADRP) of very variable expression was segregating. Positive lod scores with maxima between 1.557-5.118 at theta = 0.00, strongly suggestive of linkage, were obtained for KLK, D19S180, D19S418, and D19S254 on chromosome 19q. Recently, an ADRP locus has been mapped to the same region in a British family, in which, again, several members subjectively had no clinical evidence of the disease although they had both an affected parent and an affected child.

Adolescent↗
PubMed1995

Oguchi disease: suggestion of linkage to markers on chromosome 2q.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness. The condition is associated with fundus discolouration and abnormally slow dark adaptation. Earlier studies suggested that the 48 kD protein S antigen may be involved in the recovery phase of light transduction. Previous cytogenetic and linkage studies have localised the S antigen gene (SAG) to chromosome 2q37.1. In the present study markers which map to distal chromosome 2q were typed in an inbred Oguchi pedigree. The segregation data obtained suggested that the affected subjects are homozygous by descent for a region between D2S172 and D2S345. An intragenic SAG polymorphism was homozygous in all affected people and a recombination event suggested that SAG maps proximal to D2S345. Collectively, these findings support the hypothesis that a defect in S antigen may be responsible for Oguchi disease.

Antigens↗
PubMed1995

Myotubular myopathy in a girl with a deletion at Xq27-q28 and unbalanced X inactivation assigns the MTM1 gene to a 600-kb region.

A young girl with a clinically moderate form of myotubular myopathy was found to carry a cytogenetically detectable deletion in Xq27-q28. The deletion had occurred de novo on the paternal X chromosome. It encompasses the fragile X (FRAXA) and Hunter syndrome (IDS) loci, and the DXS304 and DXS455 markers, in Xq27.3 and proximal Xq28. Other loci from the proximal half of Xq28 (DXS49, DXS256, DXS258, DXS305, and DXS497) were found intact. As the X-linked myotubular myopathy locus (MTM1) was previously mapped to Xq28 by linkage analysis, the present observation suggested that MTM1 is included in the deletion. However, a significant clinical phenotype is unexpected in a female MTM1 carrier. Analysis of inactive X-specific methylation at the androgen receptor gene showed that the deleted X chromosome was active in approximately 80% of leukocytes. Such unbalanced inactivation may account for the moderate MTM1 phenotype and for the mental retardation that later developed in the patient. This observation is discussed in relation to the hypothesis that a locus modulating X inactivation may lie in the region. Comparison of this deletion with that carried by a male patient with a severe Hunter syndrome phenotype but no myotubular myopathy, in light of recent linkage data on recombinant MTM1 families, led to a considerable refinement of the position of the MTM1 locus, to a region of approximately 600 kb, between DXS304 and DXS497.

Adult↗
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

Gene for Simpson-Golabi-Behmel syndrome is linked to HPRT in Xq26 in two European families.

Linkage analysis was performed in 2 previously described European families segregating for the Simpson-Golabi-Behmel (SGB) syndrome. In both kindreds close linkage without recombination (zmax = 4.45 at theta = 0.00) was observed between the disease locus and the HPRT locus mapped in Xq26. These data are very similar to those (zmax = 7.5 at theta = 0.00) reported recently by others after studying a large Dutch-Canadian kindred with SGB syndrome. Compiled lod scores from the 3 families reach their maximum of 11.95 at recombination fraction of 0.00 with one lod unit support interval of 0.00-0.04.

Abnormalities, Multiple↗
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

Prenatal diagnosis and carrier detection in mucopolysaccharidosis type II by mutation analysis. A 47,XXY male heterozygous for a missense point mutation.

Identification of iduronate-2-sulphatase (IDS) gene mutations in patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) allows fast and reliable carrier detection and prenatal diagnosis. We describe here three cases of prenatal diagnosis by direct detection of the gene mutation. In addition to two affected male fetuses from two different families, a 47,XXY fetus carrying both the normal and the mutant allele was diagnosed in a third family. The latter pregnancy was carried to term and the child is obviously not affected by MPS II.

Alleles↗
PubMed1994

Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population.

Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the ar-RP-patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located on 1q31-q32.1, and RP12 (zmax = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of the family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12)-D1S53-1qter (zmax = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully.

Adult↗
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↗