OBJECTIVETo study the pattern of RET proto-oncogene mutations in two pedigrees affected with multiple endocrine neoplasia type 2A (MEN2A).

METHODSPeripheral blood samples were collected from members of the two pedigrees, with total genomic DNA extracted for polymerase chain reaction (PCR). PCR products of 7 exons of the RET proto-oncogene (including exons 8, 10, 11, 13, 14, 15, 16) which have higher mutation rates were purified and subjected to direct sequencing. Suspected mutations in the 2 probands were verified in other members of the pedigrees. To exclude other mutations, PCR products of remaining 14 exons were sequenced in the proband from pedigree 1.

RESULTSA novel heterozygous mutation, 1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene among 3 patients and 2 unaffected members from pedigree 1, while a heterozygous mutation, Cys634Arg, was detected in exon 11 among 2 patients and 1 unaffected family member from pedigree 2.

CONCLUSIONThe heterozygous 1893-1895delCGA and Cys634Arg mutations of the RET proto-oncogene probably underlie the disease in the two pedigrees. Above discovery has enriched the human gene mutation database.