Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.

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We performed a comprehensive analysis for mutations in the TSC1 gene using Southern blot analysis, and SSCP and heteroduplex analysis of amplified exons in 13 families with genetic linkage to the TSC1 region, 22 small families without linkage information, and 126 sporadic patients. 17 unique mutations were identified in 21 patients. Mutations were found in 7\13 (54 %) TSC1-linked families, 1\22 (5 %) small families without linkage, and 13 of 126 (10 %) sporadic cases. The mutations were all chain-terminating, with 14 small deletions, 1 small insertion, and 6 nonsense mutations. In families with mutations, all individuals carrying a mutation met formal diagnostic criteria for TSC, apart from a 3-year-old girl who had inherited a deletion mutation, and who had no seizures, normal intelligence, normal abdominal ultrasound, and hypomelanotic macules only on physical exam. We assessed the incidence and severity of mental retardation in the 13 sporadic patients with TSC1 mutations versus the entire sporadic cohort, and found no significant difference. The observations indicate that TSC1 mutations are all inactivating, suggest that TSC1 disease occurs in only 15-20 % of the sporadic TSC population, and demonstrate that presymptomatic TSC does occur. Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of unusual tumour-like growths (hamartomas) in a variety of organ systems

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A total of 56 Duchenne muscular dystrophy (DMD) patients and 11 Becker muscular dystrophy (BMD) patients was analyzed by extended "multiplex" amplification of the DMD/BMD gene; deletions were found in 60% of these patients. The data obtained were used to test the frameshift hypothesis and to compare the distribution of familial versus isolated cases. A significant correlation was found between deletions and isolated cases. Additional experiments were performed in order to determine the deletion breakpoints more precisely. These data are a prerequisite for carrier analysis in the respective families by detection or exclusion of aberrant cDNA fragments derived from ectopic lymphocyte RNA. This diagnostic technique is illustrated by 5 examples.

We present a technique for enhancing Fermi surface ͑FS͒ signatures in the two-dimensional ͑2D͒ distribution obtained after the 3D momentum density in a crystal is projected along a specific direction in momentum space. These results are useful for investigating fermiology via high-resolution Compton scattering and positron annihilation spectroscopies. We focus on the particular case of the ͑110͒ projection in a fcc crystal where the standard approach based on the use of the Lock-Crisp-West ͑LCW͒ folding theorem fails to give a clear FS image due to the strong overlap with FS images obtained through projection from higher Brillouin zones. We show how these superposed FS images can be disentangled by using a selected set of reciprocal lattice vectors in the folding process. The applicability of our partial folding scheme is illustrated by considering Compton spectra from an Al-3 at. % Li disordered alloy single crystal. For this purpose, high-resolution Compton profiles along nine directions in the ͑110͒ plane were measured. Corresponding highly accurate theoretical profiles in Al-3 at. % Li were computed within the local density approximation ͑LDA͒-based Korringa-KohnRostoker coherent potential approximation ͑KKR-CPA͒ first-principles framework. A good level of overall accord between theory and experiment is obtained, some expected discrepancies reflecting electron correlation effects notwithstanding, and the partial folding scheme is shown to yield a clear FS image in the ͑110͒ plane in Al-3 at. % Li.