Molecular diagnosis of multiple endocrine neoplasia type 2A

To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. A three-generation kindred with clinically and biochemically diagnosed medullary thyroid cancer. Identification of a heterozygote mutation by nucleic acid sequencing and restriction analyses. A heterozygote T-->C (Cys-->Arg) mutation at codon 618 in exon 10 of the RET proto-oncogene was identified in 4 family members who had previously been diagnosed with medullary thyroid cancer. The same mutation was also found in one of the proband's presymptomatic children who subsequently underwent a pre-emptive thyroidectomy. The genetic diagnosis was confirmed by histology. No mutations were detected in any other family members. Identification of heterozygote germline mutations in multiple endocrine neoplasia is direct, highly accurate and cost-effective. This study demonstrates that, appropriately used, molecular diagnosis can supersede conventional biochemical methods in the management of patients with inherited cancers.