Department of Geriatrics, Department of Cadres, Tong Ling People's Hospital, Tongling, Anhui 244000, China
2.
Department of Endocrinology, Wuxi No.2 People's Hospital, Wuxi, Jiangsu 214002, China
3.
Department of Endocrinology, Nanjing Municipal Chinese Traditional Medical Hospital, Nanjing, Jiangsu 210001, China
4.
Department of Pathology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Funds:
The work was supported by grant 81170747 from the National Natural Sciences Foundation of China, grant H201106 from Health Promo-tion Foundation of Jiangsu Province, grant from the Office of Human Resources and Social Security of Jiangsu Province (Peak of the Six Personnel in Jiangsu Province) to Hongwen Zhou.
Multiple endocrine neoplasia type 2A (MEN2A), a subtype of MEN2, is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A Han Chinese pedigree with MEN2A was inves-tigated following confirmation of the proband's diagnosis by pathological findings and DNA/biochemical screen-ing. DNA samples from 4 other family members were collected and exon 5, 8, 10, 11, 13, 16 and 18 of the RET proto-oncogene were sequenced and then analyzed. A missense mutation of TGG (Trp) to TGC (Cys) at codon 634 (the classic MEN2A mutation) in exon 11 of the RET gene was detected in 3 family members, including the proband. Sequencing data were compared with the human gene mutation database. Elevated serum calcitonin level was detected initially; medullary thyroid carcinoma was revealed in the 3 cases and adrenal pheochromocy-toma was also found in the proband. Elective operations were successfully performed on the adrenal and thyroid glands because of pheochromocytoma and medullary thyroid carcinoma. Our case study confirms that integrated DNA-based/biochemical screening is crucial for early diagnosis of MEN2A and is helpful in the screening of their relatives. In addition, DNA-based screening may occasionally uncover a previously unknown RET sequence.