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- Bausch, Birke, et al.
(författare)
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Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:7, s. 2784-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma.MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed.RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype.CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.
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- Klein, Richard J.T., et al.
(författare)
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Portfolio screening to support the mainstreaming of adaptation to climate change into development assistance
- 2007
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Ingår i: Climate change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 84:1, s. 23-44
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Tidskriftsartikel (refereegranskat)abstract
- The need to mainstream adaptation to climate change into development planning and ongoing sectoral decision-making is increasingly recognised, and several bilateral and multilateral development agencies are starting to take an interest. Over the past years at least six development agencies have screened their project portfolios, generally with two goals in mind: (1) to ascertain the extent to which existing development projects already consider climate risks or address vulnerability to climate variability and change, and (2) to identify opportunities for incorporating climate change explicitly into future projects. As each portfolio screening was conducted independently, the broader lessons emerging from the screenings have not been systematically analysed. In this paper we assess the screening activities to date, focusing on both the results and the methods applied. Based on this assessment we identify opportunities for development agencies to expand their current focus on the links between climate and development. Most agencies already consider climate change as a real but uncertain threat to future development, but they have given less thought to how different development patterns might affect vulnerability to climate change. The screenings undertaken have shown the need to take a comprehensive approach to adaptation and its integration into development planning and sectoral decision-making, and a number of policy initiatives have been taken to promote such integration. We provide some initial guidance as to how portfolio screening can be carried out in a way that would allow agencies to assess systematically the relevance of climate change to their ongoing and planned development projects.
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