Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting.

The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's disease (HSCR) are inherited neurocristopathies characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and gastrointestinal neuromatosis. Mutations in the RET proto-oncogene are the underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggests a founder effect for this mutation. We have observed in our and in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by HSCR. We suggest that parental imprinting may play a role in the ethiology of HSCR caused by mutations in the RET protooncogene.

Changes of muscarinic cholinergic binding by lymphocytes in Parkinson's disease with and without dementia.

We compared the muscarinic cholinergic binding in lymphocytes of 44 patients with idiopathic Parkinson's disease with 23 age-matched normal volunteers, using [3H]quinuclidinyl benzilate. In 24 patients with Parkinson's disease without dementia, binding was normal in 12, below control values in 6, whereas the remaining 6 (all on anticholinergic medication) showed very high binding. In all 20 patients with Parkinson's disease and with dementia, the binding was below control levels, indicating that in these patients, as in patients with Alzheimer's dementia, the cholinergic muscarinic binding by lymphocytes is reduced.