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Background. The multiple endocrine neoplasia type 2A gene is the RET proto-oncogene located on the long arm of chromosome 10, and many mutations within this gene have been reported.
Methods. Peripheral blood DNA was analyzed from 95 members of twelve families with multiple endocrine neoplasia type 2A and known mutations in codon 634 (of exon 11) of the RET proto-oncogene. This region was amplified by the polymerise chain reaction, followed by digestion with Cfo I, which detects restriction sites created by the most common TGC->CGC mutation and by a TGC->TGG mutation or with Rsa I, which detects a restriction site created by a TGC->TAC mutation.
Results. Diagnoses were confirmed in 39 patients; 1,5 of 56 at-risk persons were gene carriers and 41 were noncarriers. The noncarriers included seven persons who had previously undergone thyroidectomies for suspected C-cell hyperplasia but were negative for the RET mutation present in affected members of their families.
Conclusions. Identification of the specific gene alterations within families permits direct DNA diagnosis of at-risk family members. The 41 noncarriers will not require further testing nor need to be concerned about transmitting multiple endocrine neoplasia type 2A to their descendants. The normal DNA findings in seven of these persons emphasize the importance of DNA studies in patients with C-cell hyperplasia but no medullary thyroid cancer at operation.
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☆Supported in part by the Dykstra Foundation.
☆☆Presented at the Fifteenth Annual Meeting of the American Association of Endocrine Surgeons, Dearborn, Mich., April 17–19, 1994.
© 1994 Published by Elsevier Inc.