GRAIL, an omni-directional gravitational wave detector

A cryogenic spherical and omni-directional resonant-mass detector proposed by the GRAIL collaboration is described.Comment: 5 pages, 4 figs., contribution to proceedings GW Data Analysis Workshop, Paris, nov. 199

A novel CCM2 variant in a family with non-progressive cognitive complaints and cerebral microbleeds

Lobar cerebral microbleeds are most often sporadic and associated with Alzheimer's disease. The aim of our study was to identify the underlying genetic defect in a family with cognitive complaints and multiple lobar microbleeds and a positive family history for early onset Alzheimer's disease. We performed exome sequencing followed by Sanger sequencing for validation purposes on genomic DNA of three siblings with cognitive complaints, reduced amyloid-beta-42 in CSF and multiple cerebral lobar microbleeds. We checked for the occurrence of the variant in a cohort of 363 patients with early onset dementia and/or microbleeds. A novel frameshift variant (c.236_237delAC) generating a premature stop codon in the CCM2 gene shared by all three siblings was identified. Pathogenicity of the variant was supported by the presence of cerebral cavernous malformations in two of the siblings and by the absence of the variant exome variant databases. Two siblings were homozygous for APOE-ϵ4; one heterozygous. The cognitive complaints, reduced amyloid-beta-42 in CSF and microbleeds suggest preclinical Alzheimer's disease, but the stability of the cognitive complaints does not. We hypothesize that the phenotype in this family may be due to a combination of the CCM2 variant and the APOE status. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc

CHEK2 1100delC in patients with metachronous cancers of the breast and the colorectum

BACKGROUND: Development of multiple primary tumors is a hallmark of hereditary cancer. At least 1/10 of breast cancers and colorectal cancers occur because of heredity and recently the cell cycle kinase 2, CHEK2 1100delC allele has been identified at a particularly high frequency in families with hereditary breast and colorectal cancer. METHODS: We utilized the Southern Sweden population-based cancer registry to identify women with double primary breast and colorectal cancer and sequenced tumor material in order to assess the contribution of the CHEK2 1100delC to the development of such metachronous tumors. RESULTS: Among the 75 patients successfully analyzed, 2 (2.5%) carried the CHEK2 1100delC allele. which was not significantly different (p = 0.26) from the 1% (3/300) carriers identified in the control group. CONCLUSION: In summary, our data suggest that the CHEK2 1100delC is not a major cause of double primary breast and colorectal cancer in Sweden, which suggests that this patient group should not routinely be screened for the CHEK2 1100delC variant

Screening for BRCA2 mutations in 81 Dutch breast–ovarian cancer families

We have analysed 81 families with a history of breast and/or ovarian cancer for the presence of germline mutations in BRCA2 with a number of different mutation screening techniques. The protein truncation test (PTT) for exons 10 and 11 detected four different frame-shifting mutations in six of these families. Four of the remaining 75 families had given positive linkage evidence for being due to BRCA2. In these families the entire coding region was analysed by single-strand conformational polymorphism, leading to the detection of a non-sense and a splice-site mutation in two of them. While these studies were in progress, Southern analysis of BRCA1 revealed that in our study-population of 81 families, 15 families were segregating either the exon 13 or exon 22 deletion in BRCA1 (Petrij-Bosch et al (1997) Nat Genet17: 341–345). This prompted us to examine BRCA2 in the remaining 58 families by Southern analysis, using two different restriction enzymes. No aberrations were found in the restriction patterns. Thus, contrary to BRCA1, large genomic rearrangements within the BRCA2 gene do not represent a major mutation mechanism among Dutch breast cancer families. © 2000 Cancer Research Campaig