Physical mapping strategies are being employed for an analysis of the fragile X site region. Deletion breakpoints which may be close to the fragile site appear to be at a distance of at least several hundred kb from the nearest DNA probes. Further evidence is found for physical linkage between St14 (DXS52), DX13 (DXS15) and MN12 (DXS33). The data indicate differences in CG content and/or methylation levels between the distal and proximal sides of the fragile site.

Chromosome Deletion↗

PubMedDate not supplied

Mapping of a cerebellar degeneration related protein and DXS304 around the fragile site.

We have localized the gene encoding a cerebellar degeneration related (CDR) protein to a region proximal to the fragile site close to DXS98 and DXS105. This gene is polymorphic with the enzyme RsaI and therefore also provides a new genetic marker in this region. We have refined the localization of the locus DXS304 distal to the breakpoint in a patient suffering from Hunter disease. This confirms the localization of DXS304 distal to the fragile site previously suggested by linkage studies and localizes the fragile X mutation to a relatively small region between the Hunter breakpoint and the breakpoint in another hybrid B17.

Base Sequence↗

PubMedDate not supplied

Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome.

We report on a family with X-linked mental retardation (XLMR) and severe spastic paraplegia. Appearance is normal but there is severe involvement of the lower limbs (affected relatives never walked), with minimal involvement of the upper limbs and unusual MRI findings including macrogyria, white matter hypoplasia, lack of myelination and a markedly increased paramagnetic signal suggestive of iron deposition. Linkage studies documented possible linkage, with no recombination, between the disease locus and DXS424. A 7-point linkage analysis yielded a maximum LOD score of 1.9, (theta = 0.00) for three loci spanning Xq22-q25. The combination of the unusual clinical and MRI findings and the tentative localization to a region different than other XLMR syndromes with spastic paraplegia, provide good evidence that this is a new XLMR syndrome.

Adult↗

PubMedDate not supplied

Branchio-oto-renal syndrome.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder with branchial, otologic, and renal manifestations. The branchial manifestations usually are inconsequential, however the hearing impairment and renal malformations can be significant. The disease is caused by mutations in the EYA1 gene.

Branchio-Oto-Renal Syndrome↗

PubMedDate not supplied

Cell membrane signals in the mechanism of insulin action. Claude P. Brown memorial lecture.

Present evidence points to the rapid formation of one or several mediators by proteolysis initiated by insulin and, possibly, other hormones. Mediators act intracellularly at a number of subcellular sites, including cytoplasm, mitochondria, endoplasmic reticulum, cell membrane, and nucleus (figure 9). These mediators control enzymes that are controlled by covalent phosphorylation. As a result, the mediators impart an overall integrated control of metabolism. Evidence strongly suggests that the mediators are peptides. They appear to be formed by limited proteolysis from cell membrane proteins or glycoproteins and act as transmembrane signals following the binding of insulin to its receptor and the activation of the insulin-receptor complex.

Animals↗