DIRECT, NONRADIOACTIVE DETECTION OF MUTATIONS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A FAMILIES

We have designed PCR primers that permit the rapid non-isotopic detect ion of mutations in codon 634 of the RET proto-oncogene, the causative mutations in over 80% of MEN 2A and 50% of FMTC families. In this pap er we report the investigation of eleven MEN 2A families referred to t he East Anglian Regional Genetics Service. Nine of these families carr y codon 634 mutations. We were able to confirm the diagnosis of MEN 2A in twenty six affected individuals and to determine the carrier statu s of forty one individuals thought to be at risk of developing the dis ease. Of those at risk, thirty one patients lacked the familial mutati on and ten were presymptomatic carriers of MEN 2A. In five cases the d irect test proved that patients who had been treated by thyroidectomy but who lacked confirmed cancer, did not carry the familiar mutation, removing the perceived risk of MEN 2A from their children. This group included one patient who had been diagnosed as having mild C-cell hype rplasia, confirming that in MEN 2A families C-cell hyperplasia can res ult from causes other than the presence of the MEN 2A mutation.