多发性内分泌瘤病2a型家系调查——附二例报告

目的调查2例多发性内分泌腺瘤病2a型（MEN2a）患者及其家系，并复习相关文献。方法调查2例MEN2a及其家系，抽取2例先证者及先证者1家系7名成员外周血提取DNA，对RET原癌基因的第10、11外显子进行PCR扩增，用全自动测序仪进行测序分析。结果（1）经RET基因突变检查证实。2例先证者存在10q11．2外显子11（密码634）RET原癌基因发生点突变：Cys643Arg。（2）先证者1家系有3例患者，5例基因突变携带者；先证者2家系有11例患者，其中2例因肿瘤转移死亡。（3）国内MEN2a突变基因均为密码634突变，包括TGC→TGG（Cys634Trp），TGC→TAc（Cys634Tyr），TGC→CGC（Cys634Arg）和TGC→GGC（Cys634Gly）。结论应常规对所有MEN2a患者及其家系高危成员尽早进行基因突变分析和筛查，以便为临床医师和外科医师诊治提供参考。     

RET原癌基因突变致甲状腺髓样癌一个家系的研究

目的：研究1个家系中甲状腺髓样癌(medullary thyroid carcinoma,MTC)的发病与RET原癌基因突变的关系。方法：提取6名家系成员外周血DNA，采用聚合酶链反应(PCR)及直接DNA测序技术对先证标本PCR产物中的RET原癌基因第10号和11号外显子，以及另5名家系成员标本的RET原癌基因11号外显子进行分子检测。结果：在2例MTC患的外周血DNA中检测到RET原癌基因11号外显子634位密码子的点突变，即634 TGC(Cys)→CGC(Arg)，且该突变为杂合子突变。另4名表型正常的家系成员外周血DNA标本末发现上述突变。结论：RET原癌基因11号外显子634密码子点突变是该家系遗传性MTC发病的分子基础。基因检测不仅为Ⅱ型多发性内分泌腺瘤(MENⅡ)各亚型的早期诊断提供了遗传学依据，并且有助于预测家系成员患病的危险性。     

一MEN2A家系的遗传学分析及ATA2015年MTC管理指南基因检测解读

目的研究一多发性内分泌腺瘤病2A型(MEN2A)家系RET原癌基因突变位点,用于指导临床实践。方法对MEN2A综合征先证者及其家系成员的外周血提取DNA,对RET基因热点突变的第10、11外显子进行检测,并结合2015年美国甲状腺协会(ATA)发布的《甲状腺髓样癌管理指南修订版》,对相关基因检测内容进行解读。结果第11外显子634密码子存在TGC→TAC突变(CM941237),编码的氨基酸由Cys(半胱氨酸)变为Tyr(酪氨酸)。可根据RET等相关基因的突变类型区分危险等级,用于指导预防性外科治疗的选择。结论 MEN2A综合征基因突变类型的早期检测对预防性外科治疗的选择具有重大指导意义。     

一种新的FⅩⅢ基因突变导致的遗传性FⅩⅢ缺陷症

目的 对1例遗传性凝血因子ⅩⅢ（FⅩⅢ）缺陷症患者及其家系成员FⅩⅢ基因[F（13）A]进行分析，探讨其分子致病机制。方法 尿素溶解法定性检测FⅩⅢ活性，抽提外周血基因组DNA．PCR扩增FⅩⅢA基因的15个外显子及其侧翼序列，PCR产物纯化后直接基因测序，并对家系成员F（13）基因相应的突变序列进行检测。结果 先证者FⅩⅢ定性试验阳性。基因测序发现先证者F（13）A存在纯合缺失，外显子10自127067位起缺失33个核苷酸（127067del33，GI：AF418272），导致阅读框内缺失11个氨基酸（406Met-416Ala），产生了由720个氨基酸残基组成的截短型FⅩⅢA蛋白。其父母FⅩⅢ定性试验为阴性，均显示为该序列的杂合缺失突变。结论 先证者为遗传性FⅩⅢ缺陷症患者，由F（13）A外显子10缺失突变所致。该突变为国际首次报道。     

两个遗传性蛋白C缺陷症家系临床表型和基因型变化的研究

目的对两个遗传性蛋白C（PC）缺陷症家系进行临床表型和基因突变检测。方法血浆蛋白C活性（PC：A）和抗原（PC：Ag）分别用发色底物法和ELISA法测定，蛋白S活性（PS：A）和抗凝血酶活性（AT：A）用发色底物法测定。用PCR法对先证者PC基因的9个外显子及其侧翼、内含子序列进行扩增，PCR产物纯化后直接测序，检测其基因突变。仅对先证者家系成员基因突变部位的外显子及其侧翼序列进行PCR扩增和测序。突变位点经限制性内切酶酶切分析或直接测序证实。结果先证者1（Ⅱ7）的PC：A和PC：Ag分别为1．2％和0。基因测序显示，先证者1在PC基因外显子5存在C3135G杂合错义突变，致C（TGC）64W（TGG），同时在外显子7存在T6128G杂合错义突变，致F（TTC）139V（GTC）。家系成员中，先证者的父亲（Ⅰ4）和女儿（Ⅲ3）存在T6128G杂合突变，先证者的舅舅（Ⅱ）存在C3135G杂合突变，先证者丈夫（Ⅱ8）存在外显子76161-6163或6164～6166AAG（K150或K151）杂合缺失，而其女儿（Ⅲ3）亦有此突变。先证者2（Ⅲ1）的PC：A和PC：Ag分别为50．3％、1．9mg／L，基因测序显示其存在K150或K151杂合缺失，该突变遗传自其父亲。2个家系中所有成员在PC基因启动子区中存在-1654C／T、-1641A／G、-1476A／T多态性，先证者2为CC／GG／TT纯合型。限制性内切酶PSp5Ⅱ酶切分析显示T6168G不是多态性。所有成员的PS：A和AT：A均在正常范围。结论复合杂合性PC基因突变（C64W和F139V）是导致先证者1遗传性Ⅰ型PC缺陷症的原因，杂合性Lys150或151缺失突变和PC基因启动子区CC／GG／TI纯合多态性是致先证者2遗传性Ⅰ型PC缺陷症的原因。C64W为国际首次报道，F139V、K150或151缺失突变为国内首次报道。     

三个遗传性血小板无力症家系临床表型和基因表型诊断的研究

目的对3个遗传性血小板无力症（glanzmann thrombasthenia，GT）家系进行血小板膜糖蛋白Ⅱb、Ⅲa（GPⅡb／GPⅢa）基因突变的检测。方法应用PCR对先证者GPⅡb／GPⅢa基因所有外显子及其侧翼序列进行扩增；PCR产物纯化后直接测序，检测其突变基因。突变位点经直接测序证实排除基因多态性。结果3个家系的先证者PLT均正常，血小板形态分散，出血时间（BT）延长，凝血象正常，对二磷酸腺苷（ADP）、凝血酶、肾上腺素、胶原、花生四烯酸等多种诱聚剂反应低下，而对瑞斯托霉素反应基本正常；家系1和家系2先证者的血小板膜表面CD41，（GPⅡb）／CD61（GPⅢa）的含量极度降低，分别为0．16％／1．8％、0．9％／3．7％，家系3先证者的血小板膜表面GPⅡb阳性血小板为10．1％，GPⅢa阳性血小板为12．8％。免疫印迹法几乎检测不到家系1和家系3先证者的α／Ⅱb。蛋白，家系2先证者的α／Ⅱb蛋白含量明显降低。家系1先证者在GPⅡb基因存在T2255G和C2671T复合杂合突变，家系2先证者在GPⅡb基因存在A2334C纯合突变，家系3先证者在GPⅡb基因存在C1750T和69-79del复合杂合突变。结论T2255G和C2671T复合杂合突变是导致家系1先证者发生GT的原因，A2334C纯合突变是导致家系2先证者发生GT的原因，C1750T和69-79del复合杂合突变是导致家系3先证者发生GT的原因。     

HRM筛查PROC基因突变方法的建立和应用

目的 利用高分辨率熔解曲线(HRM)结合PCR技术,建立遗传性蛋白C缺陷症患者的蛋白C基基因(PROC)突变筛查方法.方法 收集仁济医院2010年4月～2011年6月收治的9例蛋白C缺陷的静脉血栓患者(经测序PROC基因均已知)及其6例确认有PROC基因缺陷的患者家属DNA标本,通过设计HRM引物,用已知PROC突变的DNA标本进行构建,建立PROC基因外显子1,2,3,7,8突变HRM筛查方法.同时对3例疑似PROC基因缺陷患者,进行该方法的验证.结果 PROC基因外显子1,2,7,8区,突变体与野生型通过HRM图形可进行区分.对3例疑似PROC基因缺陷标本,HRM均筛查出突变,经测序2例为相同外显子7区杂合突变c.565C＞T,合并外显子2区杂合同义突变c.66T＞C,另1例为外显子7区杂合缺失c.577～579del,合并外显子1区多态性位点rs1799810 A＞T.综合统计15例已知标本和3例验证标本,HRM对于PROC基因外显子1,2,7,8区准确度分别为100％,94.4％,100％和91.7％.外显子3区由于缺乏突变病例,无法构建,改为直接测序法.结论 该研究建立了HRM结合直接测序法筛查PROC基因变异的方法.该方法能较快速、方便、经济地筛查PROC变异,适用于遗传性PC缺陷症基因诊断.     

海南省71例黎、汉族葡萄糖-6-磷酸脱氢酶缺乏症患者的基因突变型分析

目的分析海南省29例汉族和42例黎族葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症患者的G6PD基因突变类型。方法采用突变特异性扩增系统法筛查海南省人群中G6PD缺乏症的G1376T、G1388A和A95G三种常见突变位点；运用DNA测序技术鉴定未知突变标本G6PD基因外显子2至外显子13的基因突变类型。结果在29例汉族G6PD缺乏症患者中，发现G1376T 11例（37．9％）、G1388A 2例（6．9％）、G1376T复合G1388A突变1例（3．4％）和G1376T复合A95G突变1例（3．4％），G1376T、G1388A、A95G三种常见突变及其复合突变共占汉族G6PD缺乏症患者的51．7％；在42例黎族G6PD缺乏症患者中，发现G1376T 25例（59．5％）、G1388A 6例（14．3％）、A95G 2例（4．8％）、G1376T复合G1388A突变4例（9．5％）和G1376T复合A95G突变1例（2．4％），G1376T、G1388A、A95G三种常见突变及其复合突变共占黎族G6PD缺乏症患者的90．5％；18例（汉族14例，黎族4例）未发现G1376T、G1388A、A95G。对这18例标本的测序发现：1例G6PD内含子5第636或637位核苷酸T缺失（IVS-5 636或637 T del）突变；2例C1311T复合IVS-11 T93C突变，其余标本未发现突变。结论G1376T和G1388A是海南省人群中最常见的基因突变型；在我国人群中存在IVS-5636或637 T del突变型；在海南省黎族人群中首次报道G1376T／A95G复合突变型。     

遗传性凝血因子Ⅶ缺陷症伴组织因子异常的研究

目的探讨1个遗传性凝血因子Ⅶ（FⅦ）缺陷症伴组织因子异常家系的临床出血机制。方法用DNA直接测序法对先证者FⅦ及组织因子（TF）基因的全部外显子及其侧翼5’和3’非翻译区进行分析，寻找突变基因。反向测序证实所发现的突变。用RT—PCR及筑巢式PCR扩增先证者FⅦ cDNA，检测FⅦ基因大的缺失和（或）插入突变。对其家系成员作突变基因检测。结果在先证者FⅦ基因启动子区检测到-55C→T杂合突变。该突变来自先证者的母亲。其姐姐也带有同样的杂合突变。其他家系成员的FⅦ基因未见突型。在先证者及所有家系成员的TF基因中均发现了9363C—T（Arg131Trp）杂合多态性，9363T基因杂合频率为2．63％。结论首次报道先证者的临床出血与FⅦ杂合突变及TF的杂合多态性有关。     

1个X-连锁迟发性脊椎骨骺发育不良家系的TRAPPC2基因突变分析

目的确定1个迟发性脊椎骨骺发育不良(spondyloepiphyseal dysplasia tarda,SEDT)家系的致病基因。方法收集先证者及家系的临床资料,提取先证者及亲属外周血DNA,用高通量测序技术对先证者的COL2A1、COL1A1、MATN3、TRAPPC2、FGFR3等189个骨骼相关基因的外显子编码区测序,对发现的致病突变进行Sanger测序验证,并对家系其他成员进行该突变的检测。结果在先证者TRAPPC2基因第5外显子上发现了1个移码突变c.271_275del CAAGA半合子缺失,为X-SEDT的致病性突变,同时发现患者母亲为该突变的携带者,而患者父亲和妹妹未检测到该突变。结论用靶向二代测序和Sanger测序结合的方法确定了1个X-SEDT家系的移码突变c.271_275del CAAGA半合子缺失,为临床遗传咨询提供了分子依据。     

Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer

The genotype and phenotype characteristics of Hungarian patients with RET proto-oncogene mutations operated on for hereditary medullary thyroid cancer (MTC) were studied. The genetic screening was performed in two centers and 40 patients with hereditary MTC or C-cell hyperplasia (CCH) from 18 unrelated families were analyzed. One patient having a mutation in exon 16 (Met918Thr) presented with the MEN2B phenotype, six patients from two families had hereditary MTC without pheochromocytoma (pheo) and primary hyperparathyroidism (PHPT), whereas 33 patients from 15 families showed the MEN2A phenotype. Two different mutations were identified in exon 10 (Cys609Tyr and Cys609Ser), five different mutations were present in exon 11 (Cys634Phe, Cys634Arg, Cys634Tyr, Cys634Trp and Cys634Ser), and two different mutations were localized in exon 14 (Val804Met and Val804Leu). Mutations in exon 10 were associated with hereditary MTC (Cys609Tyr) or with MEN2A syndrome (Cys609Ser). Mutations in exon 11 were always associated with the MEN2A phenotype. PHPT was present in one patient with mutation in exon 14 (Val804Met), whereas all other patients affected with mutations in exon 14 had hereditary MTC without PHPT and/or pheos.     

Change in the spectrum of RET mutations diagnosed between 1994 and 2006

Medullary thyroid carcinoma (MTC) is a rare calcitonin producing tumor. About 70-75% of patients with MTC have sporadic disease while the others suffer from hereditary MTC. Hereditary MTC is divided into three clinical subtypes: multiple endocrine neoplasia (MEN) type 2A is characterized by MTC, pheochromocytoma and primary hyperparathyroidism. MEN 2B is characterized by aggressive MTC, pheochromocytoma, marfanoid habitus and the presence of distinctive mucosal neuromas on the tongue, lips and subconjunctival areas as well as ganglioneuromatosis of the gastrointestinal tract. The third clinical subtype of inherited MTC, familial MTC, is defined as the presence of MTC in families without evidence of adrenal or parathyroid gland involvement. Hereditary MTC is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. The first RET germline mutations were identified in 1993 in patients with MEN 2A and FMTC. Initially a codon 634 (exon 11) mutation was found in approximately 85% of patients with MEN 2A, and germline mutations in FMTC kindreds were more equally distributed throughout the RET proto-onocogene. In about 5% of families in these earlier series, mutations did not reside in exons 10 and 11. We now report a change in the spectrum of mutations detected in the RET proto-oncogene in patients with hereditary MTC from the 'classical' mutation at codon 634 in exon 11 (level 2) to more cases with mutations in the exons 13-15 (level 1) and less aggressive disease. In our series 38.9% of mutations were level 1 mutations, 54.4% level 2, and 5.6% level 3 mutations.     

Noncardiogenic pulmonary edema as the chief manifestation of a pheochromocytoma: a case report of MEN 2A with pedigree analysis of the RET proto-oncogene.

Pheochromocytomas are rare neoplasias of the adrenal medulla which generally present with paroxysmal or sustained hypertension. Cardiogenic pulmonary edema is a common feature of these tumors, but few cases have been described with noncardiogenic pulmonary edema. We report a pheochromocytoma with the principle manifestation of noncardiogenic pulmonary edema and characterize a genetic lesion associated with the disorder. A 30-year-old man was admitted with abdominal pain and breathlessness. x-Ray examination of the chest revealed a massive, diffuse infiltration of the left lung without cardiomegaly. No paroxysmal blood pressure fluctuations or heart failure were evident during the entire course, and the infiltrate and dyspnea resolved in three days without inotropic or diuretic agents. Serum norepinephrine and epinephrine levels were elevated twenty and fifty times above normal, respectively. The patient was ultimately diagnosed with multiple endocrine neoplasia type 2A (MEN 2A). Mutations in the RET proto-oncogene have been described recently in patients with MEN 2A. Mutation analysis of selected RET exonic sequences identified a germline mutation at codon 634 in exon 11 of the RET proto-oncogene. The mutation introduces a transition encoding a non-conservative substitution from TGC (Cys) to CGC (Arg) and creates a novel restriction site recognized by HhaI. We further screened for this mutation among four of the proband's relatives by HhaI restriction analysis. One asymptomatic family member was identified who subsequently elected prophylactic total thyroid removal. Histological examination of this specimen confirmed the presence of medullary thyroid carcinoma.     

Rapid MEN 2A gene carrier identification using primer-specific PCR amplification

DNA testing is of great importance in families with multiple endocrine neoplasia (MEN) type 2A to identify non-mutant carrying family members and asymptomatic mutation carriers, and also to confirm the diagnosis in patients who already show clinical or biochemical signs of disease. Several point mutations of the RET proto-oncogene on exons 10 and 11 are associated with the disease, which is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. The aim of the present study was to develop and evaluate a simple method, which indicates the mutational status of members of families where the site of the point mutation is known. The method is illustrated by the detection of mutation TGC-->TAC of codon 611, which is one of the well-known mutations associated with MEN 2A. The method involves the PCR technique with allele-specific primers and detection of the amplified sequences with biotinylated probes. There was a clear-cut difference between the readings from affected and unaffected subjects. The subjects had been evaluated independently and all subjects harboring the mutation also had clinical disease. The method provides a simple and reliable diagnostic tool for DNA screening of members of families with a known mutation of the RET-gene.     

Hereditary medullary thyroid cancer in Slovenia – genotype-phenotype correlations

BACKGROUND: Medullary thyroid cancer (MTC) is a rare endocrine tumor that may be sporadic or inherited in settings of MEN2A, MEN2B and FMTC. Germline point mutations in the RET proto-oncogene are responsible for tumor occurrence, inheritance and great clinical variability. The aim of this study was to correlate the genotype and phenotype of patients with hereditary MTC (age at diagnosis, sex, TNM classification and clinical features). PATIENTS: Between 1997 and 2003 genetic testing was performed in 69 out of 98 patients with "sporadic" MTC. Carriage of mutation was found in 14 (20.2%) patients (index patients) and in 16 out of 31 (51.6%) of their relatives. One patient with MEN2B and codon 918 mutation was excluded from further analysis. METHODS: Genomic DNA was isolated from peripheral blood leukocytes. Exons 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were amplified in polymerase chain reactions. Point mutations of the RET gene were detected with single-strand conformation analysis and DNA sequencing. Detected mutations were confirmed with restriction enzyme analysis. RESULTS: Codon 634 mutations were detected in 15 patients (50%; aged 18-76 years; 6 families), codon 618 in nine patients (30%; aged 12-65 years; 4 families) and codon 790 in five patients (16.6%; aged 16-74 years; 3 families). The median age at diagnosis was 31 +/- 17.3, 33 +/- 15.9 and 36 +/- 23.8 years for patients with codon 618, 634 and 790 mutations. Selected by sex, females with codon mutations 618 and 634 versus 790 had median age at diagnosis of 34.5 +/- 15.6 years and 43.5 +/- 22.9 years, whereas the inverse result was observed in males (26.5 +/- 18.0 versus 16 years). The male/female ratio was 1:2 for patients with codon 618 and 634 mutations and 1:4 for patients with codon 790 mutations. Some of the data suggested correlation between specific genotypes, tumor size, stage of MTC and age at diagnosis. Pheochromocytoma (12 out of 15 patients) and primary hyperparathyroidism (6 out of 15 patients) were diagnosed solely in patients with codon 634 mutations. One patient with FMTC and Hirschprung disease was found in a family with codon 618 mutations. CONCLUSION: Correlation between tumor size, stage of MTC at diagnosis in view of patient's age, and specific genotype were indicated in our limited series and were more evident in female patients with codon 790 mutations. Later onset and a probably less aggressive course of MTC in these patients than in patients with other mutations should be considered in planning prophylactic thyroid surgery. MEN2A syndrome was related solely to codon 634 mutations.     

A novel MEN1 frameshift germline mutation in two Italian monozygotic twins

BACKGROUND: This report describes clinical, biochemical and molecular findings regarding two Italian monozygotic twins carrying a novel multiple endocrine neoplasia type 1 (MEN1) mutation inherited from their mother. METHODS: Clinical, biochemical and genetic evaluations of the above-mentioned family members were performed. RESULTS: All three members were heterozygous for a deletion involving the first nucleotide at codon 98 in exon 2 of the MEN1 gene, which results in early termination of the protein. The clinical phenotypes were as follows: one out of the two twins suffered from insulinoma and hyperparathyroidism, while the second one was asymptomatic. Furthermore, the mother suffered from hyperparathyroidism, as well as from hypergastrinemia for several years before the daughter was diagnosed of MEN-1. CONCLUSIONS: We describe a family with a new heterozygous mutation (g.292delC) in the MEN1 gene not described previously. The mutation leads to a truncated protein without activity, explaining the clinical picture of this family.     

Rapid diagnosis of MEN2B using unlabeled probe melting analysis and the LightCycler 480 instrument

Multiple endocrine neoplasia type 2B (MEN2B) is an autosomal dominant, inherited cancer syndrome. MEN2B patients have a high risk of developing medullary thyroid carcinoma, and prophylactic thyroidectomy is recommended by 6 months of age. Genetic testing can identify MEN2B patients before cancer progression. Two RET proto-oncogene mutations, in exon 15 at codon 883 (GCT>TTT) and in exon 16 at codon 918 (ATG>ACG), account for more than 98% of MEN2B cases. An assay using unlabeled probes and the LightCycler 480 instrument was developed to genotype these two common MEN2B RET mutations. Asymmetric polymerase chain reaction was used to increase ssDNA products followed by melting analysis of the unlabeled probe/ssDNA amplicon duplex. The available samples were either patient DNA of known RET genotype or artificial templates. Analysis of the codon 883 heterozygous mutation demonstrated a DeltaT(m) of 5.70 +/- 0.11 degrees C, while the codon 918 heterozygous mutation generated a DeltaT(m) of -5.72 +/- 0.11 degrees C. Samples with the targeted RET mutation genotypes were accurately detected and easily distinguishable from five other reported sequence changes using these probes. Thus, MEN2B diagnosis using unlabeled probes and the LightCycler 480 is a rapid, closed-tube method that is less time consuming and less expensive than sequencing. This assay demonstrates 100% specificity and sensitivity for the identification of RET mutations causative of MEN2B.     

多发性内分泌腺瘤病2A型（MEN2A）中嗜铬细胞瘤的临床特点及治疗

目的分析多发性内分泌腺瘤病2A型（MEN2A）家系中嗜铬细胞瘤患者的临床特点,并探讨其治疗方法。方法收集3个MEN2A家系,共有8例MEN2A患者均患有嗜铬细胞瘤,分析这8例患者高血压特点、24h尿VMA及肾上腺CT结果、嗜铬细胞瘤患病情况及治疗方法。结果8例MEN2A患者中7例有甲状腺髓样癌（87．5％）,8例有嗜铬细胞瘤（100％）,没有发现有HPT的发生,其中6例（75％）患者是以嗜铬细胞瘤起病,而且嗜铬细胞瘤中7例（87．5％）为双侧。8例患者中3例（37．5％）为持续性高血压,5例（62．5％）为阵发性发作高血压,6例（75％）24h尿VMA升高,2例（25％）高血压发作时尿VMA／Cr比值明显升高。4例患者经腹腔镜切除肿瘤,4例经开腹手术切除肿瘤,随诊7例（87．5％）良性嗜铬细胞瘤患者术后随诊均未见肿瘤复发。结论本研究结果提示MEN2A中嗜铬细胞瘤常为双侧,临床可表现为持续性高血压也常有阵发性高血压者,生化及影像学检查有助于诊断,RET基因的突变检测能使MEN2A中嗜铬细胞瘤得到早期诊治,腹腔镜下手术是MEN2A中嗜铬细胞瘤治疗的理想方法。     

多发性内分泌腺瘤病2A型(MEN2A)中嗜铬细胞瘤的临床特点及治疗

目的 分析多发性内分泌腺瘤病2A型(MEN2A)家系中嗜铬细胞瘤患者的临床特点,并探讨其治疗方法 方法 收集3个MEN2A家系,共有8例MEN2A患者均患有嗜铬细胞瘤,分析这8例患者高血压特点、24 h尿VMA及肾上腺CT结果 、嗜铬细胞瘤患病情况及治疗方法 结果 8例MEN2A患者中7例有甲状腺髓样癌(87.5%),8例有嗜铬细胞瘤(100%),没有发现有HPT的发生,其中6例(75%)患者是以嗜铬细胞瘤起病,而且嗜铬细胞瘤中7例(87.5%)为双侧.8例患者中3例(37.5%)为持续性高血压,5例(62.5%)为阵发性发作高血压,6例(75%)24 h尿VMA升高,2例(25%)高血压发作时尿VMA/Cr比值明显升高.4例患者经腹腔镜切除肿瘤,4例经开腹手术切除肿瘤,随诊7例(87.5%)良性嗜铬细胞瘤患者术后随诊均未见肿瘤复发.结论本研究结果 提示MEN2A中嗜铬细胞瘤常为双侧,临床可表现为持续性高血压也常有阵发性高血压者,生化及影像学检查有助于诊断,RET基因的突1变检测能使MEN2A中嗜铬细胞瘤得到早期诊治,腹腔镜下手术是MEN2A中嗜铬细胞瘤治疗的理想方法