Mutations of the ret protooncogene in German multiple endocrine neoplasia families: Relation between genotype and phenotype.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation

From flood basalts to the inception of oceanization: Example from the 40Ar/39Ar high-resolution picture of the Karoo large igneous province

International audienceThe Jurassic Karoo large igneous province consists of vast quantities of basaltic lava-flows, giant dike swarms and poorly dated silicic magmatism. The Karoo magmatism occurred over more than 3x106 km² and was associated with the opening of the Indian Ocean. We present new 40Ar/39Ar geochronological data concerning the easternmost part (i.e. the Mwenezi and Lebombo areas) of the Karoo province, close to the future rifted margin. These data allow documenting the final history of the province and the time elapsed between the end of the Karoo magmatism and the inception of oceanisation. This important type of information is poorly constrained for most of the large igneous provinces. Eighteen plagioclase separates yielded 14 plateau and « mini-plateau » ages obtained on 3 basaltic dikes (178.1 ± 1.1 to 177.2 ± 2.4 Ma; 2σ), 3 gabbroic (178.2 ± 1.7 to 176.8 ± 0.7 Ma) and 2 silicic (175.8 ± 0.7 to 174.4 ± 0.7 Ma) plutons and 1 rhyolitic lava-flow (177.8 ± 0.7 Ma). We also obtained three concordant plateau and mini-plateau ages ranging from 173.9 ± 0.7 Ma to 172.1 ± 2.3 Ma on the atypical E-MORB-like N-S striking Rooi Rand dikes. One dike from the Save-Limpopo N70°-oriented giant dike swarm provides a mini-plateau age of 177.7 ± 0.8 Ma in agreement with the dates previously determined on this branch and possibly assessing the same age and short duration (≤ 1-2 Myr) as for the 179 Ma giant Okavango dike swarm. New and previous selected age data obtained on the Karoo province show that the magmatism was active over ca. 10 Myr from 184 to 174 Ma. The main basaltic phase occurred mostly over the first ~5 Myr and was progressively followed by a more differentiated and less voluminous magmatism over the last 4 Myr. The easternmost Lebombo-Mwenezi long lasting magmatism is interpreted as being triggered by the progressive lithospheric extension preceding the continental disruption. The transition from rifting to oceanisation is probably illustrated by the E-MORB-like Rooi Rand dikes which are likely to be emplaced during or shortly after the final stage of the Karoo magmatism. A geodynamic evolution of the province is proposed. These data indicate that the Karoo magmatism represents an atypical province (admitting that other large igneous provinces are sufficiently known) with a long lasting and relatively low-emission rate magmatic activity. It appears from a re-evaluation of major Phanerozoic Continental Flood Basalts (CFBs), that for most of them, including the Karoo, the onset of oceanisation shortly follows (or is coeval to) the latest CFB-related activity more closely than previously thought