Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.

The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. A minority of patients with the syndrome do not have a deletion detectable with current cytogenetic techniques. Using three highly polymorphic DNA probes (pYNZ22, pYNH37.3, and p144D6) we have detected microdeletions in three MDS patients, two of whom had no visible abnormalities of chromosome 17. Loci defined by two of the DNA probes, pYNZ22 and pYNH37.3, were deleted in all three patients. The most distal locus, defined by p144D6, was present in one MDS patient, possibly defining the distal limits of the MDS region in band 17p13.3. None of these loci were absent in one case of lissencephaly without MDS.

Epinephrine-induced renin secretion is not initiated by cardiac adrenoceptors.

Experiments were designed to test the hypothesis that epinephrine may act directly on cardiac or pulmonary adrenoceptors to alter the release of a humoral substance that in turn influences renin secretion. Accordingly, anesthetized dogs were prepared with catheters for infusion of epinephrine at three sites: 1) into the aorta just distal to the left subclavian artery, 2) into the left ventricle, and 3) near the right atrium. Left renal renin secretion rates were determined before, during, and after 30-min infusions of epinephrine at each site in each animal; the order of the infusions was randomized. At epinephrine infusion rates of 15 and 75 ng.kg-1.min-1, epinephrine-induced changes in renin secretion rates were dose dependent but were independent of the site of infusion. These data do not support the hypotheses that either pulmonary or cardiac adrenoceptors are involved in the initiation of epinephrine-induced renin secretion. In additional experiments, an isolated canine heart was perfused with femoral arterial blood from an experimental dog, and the coronary venous effluent was returned to the experimental dog via the femoral vein. Intravenous epinephrine infusion at 50 ng.kg-1.min-1 increased plasma renin activity nearly 1.5-fold. In contrast, plasma renin activity did not increase during infusion of epinephrine at 5 ng.kg-1.min-1 directly into the coronary perfusate of the isolated heart. Coronary perfusate epinephrine concentration was 699 +/- 71 pg/ml (mean +/- SE) during intravenous infusion and was 851 +/- 121 pg/ml during direct infusion of epinephrine into the coronary perfusate. We conclude that cardiac adrenoceptors do not participate in the initiation of epinephrine-induced renin secretion.

Inverted duplication of JH associated with chromosome 14 translocation and T-cell leukemia in ataxia-telangiectasia.

A specific 14q32 breakpoint is observed in a homologous chromosome 14 translocation [t(14;14)q12q32] occurring in the T-cells of about 10% of patients with ataxia-telangiectasia (AT). To investigate whether the 14q32 breakpoint in AT occurs within the immunoglobulin gene cluster as is frequently detected in B-cell lymphoma, immunoglobulin clones were hybridized to Southern blots of DNA isolated from the T-cells of two AT patients with this chromosome 14 translocation. The 14q32 translocation breakpoints in these patients are apparently not within JH, S mu, C mu, S alpha-1 or -2, or C alpha-1 or -2, but one of the patients has an inverted duplication of at least 26 kilobases (kb) of the C mu region, with an associated 5' flanking deletion. The point of origin of the inverted duplication is within JH near the recombination signal for the J4 gene. This suggests that normal JH recombination mechanisms may have played a role in the development of this 14q32 chromosomal aberration. The presence of AT chromosomal breakpoints near other rearranging genes suggests a role for exaggerated recombination in the pathogenesis of chromosomal instability in AT.