The Spectrum of NF1 Mutations in Korean Patients with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in humans. NF1 is caused by mutations in the NF1 gene which consists of 57 exons and encodes a GTPase activating protein (GAP), neurofibromin. To date, more than 640 different NF1 mutations have been identified and registered in the Human Gene Mutation Database (HGMD). In order to assess the NF1 mutational spectrum in Korean NF1 patients, we screened 23 unrelated Korean NF1 patients for mutations in the coding region and splice sites of the NF1 gene. We have identified 21 distinct NF1 mutations in 22 patients. The mutations included 10 single base substitutions (3 missense and 7 nonsense), 10 splice site mutations, and 1 single base deletion. Eight mutations have been previously identified and thirteen mutations were novel. The mutations are evenly distributed across exon 3 through intron 47 of the NF1 gene and no mutational hot spots were found. This analysis revealed a wide spectrum of NF1 mutations in Korean patients. A genotype-phenotype correlation analysis suggests that there is no clear relationship between specific NF1 mutations and clinical features of the disease

The Human Genome Puzzle – the Role of Copy Number Variation in Somatic Mosaicism

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual. A unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations

Size quantization effects in thin film Casimir interaction

We investigate the role of size quantization in the vacuum force between metallic films of nanometric thickness. The force is calculated by the Lifshitz formula with the film dielectric tensor derived from the one-electron energies and wavefunctions under the assumption of a constant potential inside the film and a uniform distribution of the positive ion charge. The results show that quantization effects tend to reduce the force with respect to the continuum plasma model. The reduction is more significant at low electron densities and for film size of the order of few nanometers and persists for separation distances up to 10 nm. Comparison with previous work indicates that the softening of the boundary potential is important in determining the amount of the reduction. The calculations are extended to treat Drude intraband absorption. It is shown that the inclusion of relaxation time enhances the size quantization effects in the force calculations

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