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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Prediction of affected MEN2A gene carriers by DNA linkage analysis for early total thyroidectomy: a progress in clinical screening program for children with hereditary cancer syndrome.

The gene predisposing to multiple endocrine neoplasia type 2A (MEN 2A) has been assigned to chromosome 10, and affected gene carriers can be identified before the development of associated malignancy in some informative families. We applied these advances in gene mapping to clinical screening for possible pediatric surgery. A family with MEN 2A, consisting of 88 members and their spouses, was studied to test the reliability of the provocation of plasma calcitonin with pentagastrin and the possibility of DNA diagnosis of mutated gene carriers with DNA probes closely linked to the MEN2A gene including RBP3 and FNRB genes. Nineteen of the 88 were diagnosed as MEN 2A carriers. Twelve of them were treated surgically and the others died of medullay thyroid carcinoma (MTC) or pheochromocytoma. A strikingly sensitive response of calcitonin was observed in all those with MTC. The genotypes cosegregating with the abnormal allele at MEN2A in this family could be deduced from clinically established affected members. The early detection of gene carriers allows us to concentrate our screening efforts on children at high risk and to release non gene carriers from repeated unnecessary testing. MEN2A is one of the first cancer syndromes for which DNA screening permits early detection of members at high risk.[1]


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