Congenital hyperinsulinism caused by mutations in ABCC8 (SUR1) gene

Congenital hyperinsulinism is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. We report a 2.5 year old girl with severe congenital hyperinsulinism. Mutation analysis showed that the child is a compound heterozygote for two missense mutations in the ABCC8 gene.     

Use of multicolour chromosome painting to identify chromosomal rearrangements in human lymphocytes exposed to bleomycin: A comparison with conventional cytogenetic analysis of giemsa-stained chromosomes

Exchange aberrations induced by bleomycin were identified by multicolour fluorescence in situ hybridisation (FISH) with probes for chromosomes 1, 2, and 3. The frequency and distribution of aberration types were compared to conventional metaphase analysis of Giemsa-stained chromosomes from the same human lymphocyte cultures. The total percentage of exchanges detectable by painting three pairs of chromosomes with separate colours was calculated as 40%. Giemsa staining revealed predominantly asymmetric chromosome exchanges, which are expected to comprise 50% of the total induced exchanges. Genomic exchange frequencies were, therefore, determined by multiplying the observed frequencies from FISH analysis by 2.5 and the number of asymmetric exchanges identified in Giemsa-stained slides by 2.0. By these calculations, the genomic exchange frequency calculated from chromosome painting exceeded that estimated by Giemsa-staining. This difference was due to the identification by chromosome painting of a unique class of cells in which chromosomes had undergone complex exchanges (nonreciprocal exchanges involving multiple mutual sites). The percentage of cells exhibiting exchanges was similar for both methods. © 1995 Wiley-Liss, Inc.     

Visual cortical lesions abolish the use of motion parallax in the Mongolian gerbil

Summary Mongolian gerbils received lesions of either the visual cortex, pretectal nuclei, superior colliculus or a sham operation. Visual distance estimation was tested by means of a jumping task on which gerbils have previously been shown to employ motion parallax information generated by head movements. Videotaped jumps were analyzed to determine latency to jump, jump distance, and head movement frequency. While all of the lesion groups showed some changes in performance, the most severe deficits in jump accuracy were seen after the visual cortical lesions. In none of the lesion groups, however, were head movements abolished. The results suggest that the visual cortex subserves a critical aspect of dynamic distance estimation but that the motor program for generating head movements is located elsewhere.     

Phlegm production and lung function among cigarette smokers changing tar groups during the 1970s.

In 1971-3 data on smoking habits, cigarette brand smoked, morning phlegm production, and lung function were recorded for factory workers as part of the Heart Disease Prevention Project. These men were reassessed in 1984 and those who had always smoked cigarettes from the same tar group were compared with those who had dropped one tar group (mean decreases of 6.6 mg tar, 0.1 mg nicotine) and two tar groups (mean decreases of 11.9 mg tar, 0.5 mg nicotine). Over the 13 years, men who had dropped one tar group were significantly more likely (p less than 0.05) to stop producing phlegm, but the effect was less marked for those who had dropped two tar groups. The mean fall in FEV1 was similar in all three groups, but 95% confidence limits showed that although dropping one tar group could be associated with at most a saving of 84 ml over the follow up period, there could be little extra benefit from dropping two tar groups. In 1984, all three groups of smokers excreted similar amounts of nicotine metabolites in the urine, suggesting that men who had dropped two tar groups compensated for the reduced nicotine yield of their cigarettes. This could account for the lack of a dose response relationship between reduction in the tar yield of cigarettes and cessation of phlegm and fall in FEV1.     

Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway,cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis

The spondylocostal dysostoses (SCD) are a group of disorders characterised by multiple vertebral segmentation defects and rib anomalies. SCD can either be sporadic or familial, and can be inherited in either autosomal dominant or recessive modes. We have previously shown that recessive forms of SCD can be caused by mutations in the delta-like 3 gene, DLL3. Here, we have sequenced DLL3 in a series of SCD cases and identified 12 mutations in a further 10 families. These include 10 novel mutations in exons 4–8, comprising nonsense, missense, frameshift, splicing, and in frame insertion mutations that are predicted to result in either the truncation of the mature protein in the extracellular domain, or affect highly conserved amino acid residues in the epidermal growth factor-like repeats of the protein. The affected cases represent diverse ethnic backgrounds and six come from traditionally consanguineous communities. In all affected subjects, the radiological phenotype is abnormal segmentation throughout the entire vertebral column with smooth outlines to the vertebral bodies in childhood, for which we suggest the term "pebble beach sign". This is a very consistent phenotype-genotype correlation and we suggest the designation SCD type 1 for the AR form caused by mutations in the DLL3 gene.