The clinical features of multiple endocrine neoplasia type 2A (MEN2A)and ret proto-oncogene mutation study

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YAO Bin(Department of Endocrinology,First Affdiated Hospital of Sun Yat-Sen niversity,Guangzhou 510080,China)
LIU Xue(Department of Endocrinology,First Affdiated Hospital of Sun Yat-Sen niversity,Guangzhou 510080,China)
DONG Ting-ting(Department of Endocrinology,First Affdiated Hospital of Sun Yat-Sen niversity,Guangzhou 510080,China)
Journal Title:
Volume 2, Issue 10, 2008
Key Word:
Multiple endocrine neoplasia type 2A;BET proto-oncogene;Deletion mutation

Abstract´╝Ü Objective To investigate the molecular pathogenesis of multiple endocrine neoplasia 2A (MEN2A) ,three unrelated families from mainland China were studied. Methods Three unrelated families,among of which 8 were clinically diagnosed MEN2A patients.There were 28 subjects in the three families consented to perform the gene scanning.Genomic DNA of the 28 subjects were extracted from peripheral leukocytes.The 21 exons of the RET proto-oncogene were amplified using polymerase chain reaction methed,and the products were detected by direct sequencing. Further cloning and sequencing were performed for novel mutation. The mutated loci were also screened in the corresponding family members. All the identified mutations were compared with known PET proto-oncogene mutations in human gene mutation datahase in cardiff.Results In family 1, a C634R mutation at exon 11 of the BET proto-oncogene was detected,while C634Y at the same locus was found in family 2. A novel heterozygous mutation of 3-bp (GAC) deletion at coden 631 (del D631)of exon 11 was identiffed in the 4 MEN2A patients of family 3, leading to a change of sequence from TGCGACGAGCTG to TGCGAGCTG,resulting in the deletion of an asparagine at the locus.Medullary thyroid carcinoma(MTC)was found in 7(87.5%)patients,and pheochromocytoma was found in all(100%)of the 8 MEN2A patients. Hyperplasia or adenoma of the parathyroid gland was not found in any of these cases. Among them, pheochromocytoma was the initial demonstration of the syndrome in 6 patients(75% ) ,and bilateral pheochromocytomas were found in 7 of them(87. 5%).ConclusionThe study indicated that there was C634Y mutation relating to MEN2A syndrome,as well as heterozygous deletion mutation at D631 of exon 11,the latter of which was the first report to our knowledge.

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