目的:分析讨论RET原癌基因Y606C这一罕见突变所致家族性甲状腺髓样癌(familial medullary thyroid carcinoma,FMTC)的临床生物学特点。方法:对先期确诊的1个携带RET原癌基因Y606C种系突变的FMTC家系成员进行RET基因种系突变筛查,同时行血清降钙素、甲状旁腺素、颈腹部超声等相关临床检查,对患病成员和携带者给予临床干预,并总结分析上述病例临床生物学特点。结果:包括先证者在内,该家系中10例参与基因筛查,发现6例携带RET基因第10外显子Y606C突变。其中3例确诊为FMTC患者(含先证者),均为女性,平均发病年龄50.0(47~53)岁。发病成员临床均表现为甲状腺肿物伴降钙素升高,未发现甲状旁腺和肾上腺病变。2例行全甲状腺切除术,1例行患侧腺叶切除术。术后病理均确诊为甲状腺髓样癌,其中2例病理分期均属早期,术后随访期间均达生化治愈。家系中另有3例为突变携带者,平均年龄33.0(15~55)岁。其中2例颈部超声均提示甲状腺肿物(考虑良性),另1例颈部超声未见异常。除1例拒绝降钙素检测外,其余2例血清降钙素均正常范围,建议定期复查。结论:RET原癌基因Y606C突变可以导致FMTC发病,家系成员发病平均年龄较大,肿瘤分期较早,生化治愈率高,预后较好;家系成员基因检测结合颈部超声和降钙素检查有利于甲状腺髓样癌的早期诊断;对于无症状Y606C突变携带者,应根据其降钙素水平及颈部超声检查情况实施个体化临床处置。 OBJECTIVE: To analyze and discuss the clinical biological features of familial medullary thyroid carcinoma (FMTC) caused by this rare mutation of RET proto-oncogene Y606C. Methods: The mutation of RET gene was screened in a previously diagnosed FMTC family member carrying the RET proto-oncogene Y606C germline mutation. Serum calcitonin, parathyroid hormone, cervical and abdominal ultrasound and other related clinical tests were performed at the same time. The disease members and carriers to give clinical intervention, and summarize the clinical case of the above biological characteristics. Results: Including probands, 10 cases of this family were involved in gene screening and 6 cases were found to carry Y606C mutation of exon 10 of RET gene. Among them, 3 were diagnosed as FMTC patients (including probands), all of whom were female, with an average age of onset of 50.0 (47-53 years). The incidence of clinical members showed thyroid tumor with calcitonin increased, no parathyroid and adrenal lesions were found. 2 cases of total thyroidectomy, 1 case of ipsilateral lobectomy. Postoperative pathology were diagnosed as medullary thyroid carcinoma, of which 2 cases of pathological stage are early, were up to follow-up biochemical cure. Another three cases of family members were mutation carriers, with an average age of 33.0 (15-55 years). Among them, 2 cases of cervical ultrasound showed thyroid mass (benign), and the other 1 case showed no abnormality of cervical ultrasonography. In addition to 1 case refused to test calcitonin, the other two cases of serum calcitonin were normal range, it is recommended regular review. CONCLUSIONS: The mutation of RET oncogene Y606C leads to the onset of FMTC. The incidence of FMTC is higher in pedigrees with earlier stage of tumor, higher biochemical cure rate and better prognosis. Family member gene test combined with neck ultrasound and calcitonin is helpful Early diagnosis of medullary thyroid carcinoma; for asymptomatic carriers of Y606C mutation, should be based on their calcitonin levels and neck ultrasound examination of the implementation of individualized clinical treatment.