[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.
Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Yu-Lin
YL
Zhou
Shao-Xing
SX
Zhu
Jian-Jun
JJ
Li
Jing-Bo
JB
Liu
Min
M
Yin
Bu-Yun
BY
Xiao
Chao-Li
CL
Yu
Li-Ming
LM
Wang
Li-Qun
LQ
Gu
Bin
B
Cui
Guang
G
Ning
Xiao-Ying
XY
Li
Yong-Ju
YJ
Zhao
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