[The clinical patterns and RET proto-oncogene in fifteen multiple endocrine neoplasia type 2A pedigrees].
OBJECTIVE
To detect the phenotype and rearranged mutations during transfection of RET proto-oncogene in fifteen multiple endocrine neoplasia type 2A (MEN2A) probands and their family members.


METHODS
Totally 119 family members of the fifteen MEN2A pedigrees were recruited. Total genomic DNA was extracted from peripheral blood for PCR. PCR products of exon 8, 10, 11, 13, 14, 15 and exon16 of the RET proto-oncogene were purified and direct gene sequencing was performed.


RESULTS
The germline mutations of RET proto-oncogene were detected in 49 members of the fifteen MEN2A pedigrees. Among them, 37 patients had MEN2A phenotype and the remaining 12 were gene carriers. The mean age at which the members of the former group were diagnosed as MEN2A was significantly later than those of the latter group [(43.0 +/- 13.9) yr vs (9.8 +/- 7.4) yr, P < 0.01]; The incidences of medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and hyperparathyroidism (HPT) in 37 MEN2A patients were 91.9%, 56.8% and 10.8%; Five germline mutations which all located in codon 634 of exon11 in RET proto-oncogene were detected in the fifteen MEN2A pedigrees. They were C634W (13.3%), C634Y (46.7%), C634R (26.7%), C634F (6.7%) and C634S (6.7%); Through the analysis of the genotype-phenotype of the 37 MEN2A patients, no statistic significance was found in the age of diagnose for MEN2A, the incidence of PCC, the percentage of cervical lymph node metastasis and the five different genotypes.


CONCLUSIONS
The mean age at which the 37 patients of the fifteen MEN2A pedigrees were diagnosed was older than that reported in the overseas literatures. The occurrence of MTC in MEN2A patients is earlier than that of PCC and HPT. The incidences of MTC and PCC are basically consistent with those in the overseas archives, while the incidence of HPT is lower than that in the corresponding report. The detected mutations of RET proto-oncogene in MEN2A patients were all located in codon 634, being simpler than that in foreign reports.
Zhou
Yu-Lin
YL
Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Zhu
Shao-Xing
SX
Li
Jian-Jun
JJ
Liu
Jing-Bo
JB
Yin
Min
M
Xiao
Bu-Yun
BY
Yu
Chao-Li
CL
Wang
Li-Ming
LM
Gu
Li-Qun
LQ
Cui
Bin
B
Ning
Guang
G
Li
Xiao-Ying
XY
Zhao
Yong-Ju
YJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human