[DelD631: a novel mutation of the RET proto-oncogene in multiple endocrine neoplasia type 2A (MEN2A)].

OBJECTIVE: To detect RET mutations in a rare Chinese big family with Multiple endocrine neoplasia type 2A (MEN2A).

METHODS: One MEN2A family, including the proband, have 22 members of two generations, it is a rare big family in modern Chinese families. The DNAs of the 22 members from the family including 4 patients were extracted from blood leukocytes, PCR and gene sequencing of PCR products by an automated DNA sequencer were applied to scan the exon10 and 11 of RET proto-oncogene. Sequencing results were compared with the Pubmed's. Clone sequencing was adopt to further confirm the results, then verifying the novel mutation through the human gene mutation database at the institute of medical genetics in cardiff. Invitrogen biotechnology company (Shanghai) provided the technology of clone sequencing.

RESULTS: A novel deletion mutation of D631 (GAC) (del D631) was detected in exon11 of the RET proto-oncogene in 4 MEN2A patients of the family, this rare deletion mutation of D631 (GAC) lead base sequence of TGC(angle)GACGAGCTG change to TGCGAGCTG. Besides 4 MEN2A patients, the son of II6 (the first class relative) was found to be a carrier of delD631 mutation.

CONCLUSION: A novel deletion mutation (del D631) of RET proto-oncogene was detected in the family with MEN2A and it has never been reported before in the world. DelD631 may be related to the late onset of MEN2A compared to the cysteine mutations and pheochromocytoma might be the first manifestation prior to the development of MTC.