Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients

Tuberous sclerosis (TSC) is an autosomal dominant condition with characteristic skin lesions, mental handicap, seizures and the development of hamartomas in the brain, heart, kidneys and other organs. Linkage studies have shown locus heterogeneity with a TSC gene mapped to chromosome 9q34 and a second, recently identified on 16p13.3. We have analysed DNA markers in eight hamartomas and one tumour from TSC patients and found allele loss on 16p13.3 in three angiomyolipomas, one cardiac rhabdomyoma, one cortical tuber and one giant cell astrocytoma. We suggest that the TSC gene on 16p13.3 functions like a tumour suppressor gene, in accordance with Knudsen's hypothesis

Feasibility, Interrater Reliability and Internal Consistency of the German Environmental Audit Tool (G-EAT)

Dementia-specific environmental design has the potential to positively influence capabilities for daily living and quality of life in people with dementia living in nursing homes. To date, no reliable instrument exists for systematically assessing the adequacy of these built environments in Germany. This study aimed to test the adapted version of the Environmental Audit Tool—High Care (EAT-HC)—the German Environmental Audit Tool (G-EAT)—with regard to its feasibility, interrater reliability and internal consistency. The G-EAT was applied as a paper-pencil version in the German setting; intraclass correlation coefficients at the subscale level ranged from 0.662 (III) to 0.869 (IV), and 42% of the items showed at least substantial agreement (Cohen’s kappa ≥ 0.60). The results indicate the need to develop supplementary material in a manual that illustrates the meaning of the items and practical implications regarding dementia-specific environmental design. Furthermore, the intersectionality of built and physical environments must be considered when interpreting G-EAT results in future research and applications to residential long-term care practice

Nearby stop codons in exons of the neurofibromatosis type 1 gene are disparate splice effectors.

Stop mutations are known to disrupt gene function in different ways. They both give rise to truncated polypeptides because of the premature-termination codons (PTCs) and frequently affect the metabolism of the corresponding mRNAs. The analysis of neurofibromin transcripts from different neurofibromatosis type 1 (NF1) patients revealed the skipping of exons containing PTCs. The phenomenon of exon skipping induced by nonsense mutations has been described for other disease genes, including the CFTR (cystic fibrosis transmembrance conductance regulator) gene and the fibrillin gene. We characterized several stop mutations localized within a few base pairs in exons 7 and 37 and noticed complete skipping of either exon in some cases. Because skipping of exon 7 and of exon 37 does not lead to a frameshift, PTCs are avoided in that way. Nuclear-scanning mechanisms for PTCs have been postulated to trigger the removal of the affected exons from the transcript. However, other stop mutations that we found in either NF1 exon did not lead to a skip, although they were localized within the same region. Calculations of minimum-free-energy structures of the respective regions suggest that both changes in the secondary structure of the mRNA and creation or disruption of exonic sequences relevant for the splicing process might in fact cause these different splice phenomena observed in the NF1 gene

Coupling of solvent semimicroextraction with capillary electrophoresis using ethyl acetate as sample matrix

10.1002/(SICI)1522-2683(20000201)21:3<573Electrophoresis213573-578ELCT