摘要
目的 对多发性内分泌腺瘤2A型(MEN2A)1个家系进行临床调查及RET原癌基因突变位点筛查,明确疾病诊断、分型,以指导治疗、预防及改善预后。方法 对1个包括6名甲状腺髓样癌先证者在内的共36位成员的MEN2A家系进行临床资料调查,并提取28位家系成员(1位先证者未采血)外周血基因组DNA,对RET基因的第8、10、11、13、14、15、16外显子进行PCR扩增,产物直接测序。结果 RET基因各外显子PCR扩增结果显示,13名家系成员存在RET原癌基因10号外显子错义突变杂合错义突变c.1852T>A,导致618位半胱氨酸(TGC)变为丝氨酸(AGC)(Cys618Ser),其中包括5名先证者及8名家系成员。12名RET基因Cys618Ser突变携带者家系成员均有甲状腺超声改变,并伴随降钙素水平升高。而RET基因Cys618Ser野生型携带者家系成员降钙素水平均正常。病史分析证实2名甲状腺髓样癌先证者伴甲状旁腺功能亢进症,1例RET基因Cys618Ser突变携带者家系成员合并嗜铬细胞瘤,该家系最终确诊为MEN2A。结论 RET基因检测对MEN2A家系患者治疗和随访有指导作用,对无症状携带者的诊断和治疗具有指导价值。降钙素水平与RET原癌基因突变Cys618Ser之间具有良好的临床相关性。临床上疑诊患者应及时进行筛查。
Objective To investigate the clinical features and gene analysis of one pedigree with multiple endocrine neoplasia type 2A(MEN2A) so as to clarify the diagnosis and classification of the disease,guide treatment and prevention,and improve prognosis.Methods The clinical data of a 36-member MEN2A family,including 6 probands,with medullary thyroid carcinoma,were investigated,and the peripheral blood genomic DNA of 28 family members(blood sample of one proband was not collected)was extracted.PCR amplification was performed on exons 8,10,11,13,14,15 and 16 of the RET gene,and the products were directly sequenced.Results Review of the medical history showed that two probands with medullary thyroid carcinoma were accompanied with hyperparathyroidism,and one family member had pheochromocytoma.The RET gene mutation test confirmed that 13 family members,consisting of 5 probands and 8 family members,had the RET proto-oncogene exon 10 missense mutation.The heterozygous missense had mutation c.1852T>A,leading to the conversion of cysteine(TGC)at position 618 to serine(AGC)(Cys618Ser).All subjects carrying RET gene Cys618Ser mutation had abnormal thyroid ultrasound change,accompanied with elevated calcitonin levels.Subjects carrying wild type of RET gene had normal calcitonin levels.The family was finally diagnosed with MEN2A by RET gene detection.Conclusion RET gene detection plays key role in the diagnosis and treatment of patients with MEN2A family and has guiding value in the follow-up and prognosis of asymptomatic carriers.There is a positive correlation between calcitonin level and the RET protooncogene mutation Cys618Ser.Patients suspected of MEN2A should be screened in time.
作者
龚晓娟
李和平
万沣霆
樊丽娅
刘淑
刘霄炫
李雨欣
郭辉
贺雅毅
GONG Xiaojuan;LI Heping;WAN Fengting;FAN Liya;LIU Shu;LIU Xiaoxuan;LI Yuxin;GUO Hui;HE Yayi(Department of Endocrinology and Metabolism,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;College of Medicine and Forensics,Health Science Center of Xi’an Jiaotong University,Xi’an 710061,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2022年第4期566-573,共8页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
陕西省重点研发计划一般项目(No.2017SF-171,2022SF-103)。
