7例完全型雄激素不敏感综合征患者的临床及遗传学分析

目的:探讨完全型雄激素不敏感综合征(CAIS)患者的临床和分子遗传特征。方法:收集7例CAIS患者及家族相关成员的临床资料,提取外周血全基因组DNA,用特异性引物-聚合酶链反应(PCR)扩增AR基因的8个外显子,扩增产物Sanger测序后与基因库中正常人的序列进行比对,查找可能存在的致病突变。应用Mutation taster、PolyPhen-2等生物信息学软件预测突变对蛋白功能的影响。结果:7例CAIS患者的AR基因均检测到突变,并且在家系中共分离,其中有4个突变未报道过:p.Y764N、p.Q876X、p.A356Efs*123、p.S704R。3例行腹腔镜探查术及性腺活检,病理检查结果证实性腺为睾丸。结论:CAIS患者常因原发闭经就诊而被发现,多数存在异常性激素水平,家系中常有多例患者,呈X连锁隐性遗传模式。AR基因的检测有助于CAIS患者的确诊并有助于CAIS家庭的生殖咨询。     

生殖系统原发性非霍奇金淋巴瘤的临床病理特征和免疫表型检测

目的观察生殖系统原发性非霍奇金淋巴瘤的临床病理表现及免疫表型,并分析其与预后的关系。方法回顾性分析43例女性生殖系统原发性非霍奇金淋巴瘤的临床病理资料,按WHO（2001年）关于淋巴造血组织肿瘤的分类标准进行病理类型的分类,采用免疫组化染色、原位杂交及PCR技术分别检测其免疫表型、EB病毒感染及免疫球蛋白重链基因重排。采用Cox回归模型对生殖系统原发性非霍奇金淋巴瘤的预后进行多因素分析。结果（1）原发灶部位：卵巢24例,子宫内膜3例,宫颈10例,阴道2例,外阴4例;（2）临床分期：Ⅰ期12例,Ⅱ期9例,Ⅲ期22例;（3）病理类型：经病理活检、免疫组化、原位杂交及PCR技术检测结果显示,弥漫性大B细胞淋巴瘤37例（86％）,伯基特淋巴瘤和非特指外周T细胞淋巴瘤各3例;（4）预后分析：乳酸脱氢酶水平增高、临床Ⅲ期、弥漫性大B细胞淋巴瘤及单纯手术治疗患者的生存率明显低于乳酸脱氢酶水平正常、临床Ⅰ和Ⅱ期、伯基特淋巴瘤和非特指外周T细胞淋巴瘤、手术＋化疗和手术＋放化疗者（P〈0．05）。Cox回归模型多因素分析显示,乳酸脱氢酶水平、临床分期、病理类型及治疗方案均为影响原发性非霍奇金淋巴瘤患者预后的独立因素（P〈0．05）。结论病理活检、免疫组化、原位杂交及PCR技术检测对生殖系统原发性非霍奇金淋巴瘤的诊断和鉴别诊断具有重要作用。乳酸脱氢酶水平、临床分期、病理类型及治疗方案均为女性生殖系统原发性非霍奇金淋巴瘤的独立预后因素。     

NR5A1基因突变的46,XY性发育异常合并肥胖及高胰岛素血症一例

46,XY性发育异常（disorders of sex development,DSD）是一种遗传学性别、表型性别和性腺性别不一致的先天性疾病,确诊该病的关键是基因检测。回顾分析1例46,XY DSD患者,患者社会性别为女性,因查体发现性腺发育异常就诊。患者46,XY DSD合并肥胖及高胰岛素血症,致病基因为类固醇生成因子-1(steroidogenic factor 1,SF-1,又称NR5A1),突变位点为c.1095＿1096insTCGG(p.Q366Sfs*22),对该基因进行遗传学分析,该位点所致的基因突变可能与肥胖及糖尿病相关。行腹腔镜双侧隐睾切除术+外阴整形术+阴蒂切除术,维持患者女性社会性别。从遗传学角度检测病因可为46,XY DSD的临床诊治提供指导及依据。     

上皮性卵巢癌患者血清FOLR1、Smac水平与患者临床病理特征及预后的关系

目的 分析上皮性卵巢癌(EOC)患者血清叶酸受体1(FOLR1)、第2个线粒体衍生半胱氨酸蛋白酶激活因子(Smac)水平与病理参数及预后的关系.方法 选择148例经病理确诊为EOC的患者作为EOC组,卵巢良性肿瘤50例及体检健康女性50例作为对照1组、对照2组,分析EOC患者血清FOLR1、Smac水平与病理特征及近期...     

细胞核增殖相关抗原ki67和bcl-2、bax与恶性卵巢上皮性肿瘤临床病理及预后的关系

目的研究细胞核增殖相关抗原ki67和凋亡抑制基因bcl-2 、促凋亡基因bax与恶性卵巢上皮性肿瘤临床病理及预后的关系.方法采用免疫组化SP法检测85例卵巢上皮性肿瘤中ki67、bcl-2、bax表达情况.结果①ki67指数在恶性卵巢上皮性肿瘤中显著高于良性及交界性肿瘤;与恶性卵巢上皮性肿瘤组织学分级呈正相关,与预后呈负相关.②bax表达水平在卵巢恶性肿瘤组中高于良性组,与恶性卵巢上皮性肿瘤组织学分级呈负相关,与预后呈正相关;bcl-2表达水平在恶性组中高于良性组及交界组;高分化组中bcl-2∶bax≤1的患者所占比例高于中、低分化组,bcl-2∶bax≤1患者预后较好.③恶性卵巢上皮性肿瘤中ki67指数与bax表达负相关,与bcl-2表达及bcl-2∶bax比值正相关;低增殖高凋亡易感组预后好于高增殖低凋亡易感组.④临床分期和bax表达水平是影响恶性卵巢上皮性肿瘤患者预后的主要因素.结论ki67可作为评价卵巢肿瘤生物学行为及预后的指标,bcl-2、bax相互作用,对恶性卵巢上皮性肿瘤的发生、发展及预后中起一定作用,高增殖低凋亡易感性促使肿瘤恶性发展,bax为恶性卵巢上皮性肿瘤患者的保护因素.     

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2?mg 17β-estradiol/1?mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4?mg/dl versus 40.1?mg/dl, p?=?0.019) while lowering TG (166?mg/dl versus 109?mg/dl, p?=?0.026) and AIP (0.24 versus 0.04, p?=?0.007). No changes were noted in TC and LDL (215.7?mg/dl versus 192.25?mg/dl and 87.46?mg/dl versus 76.35?mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05?ng/ml versus 2.20?ng/ml, p?=?0.002) and E-selectin (73.98?ng/ml versus 56.73?ng/ml, p?=?0.004). No change was observed in Thrombomodulin and vWf (11.76?ng/ml versus 13.90?ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p?=?0.003), while only carotid bulb IMT decreased significantly (0.65?mm versus 0.60?mm, p?=?0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.     

Identification of a mutant allele of the androgen receptor gene in a family with androgen insensitivity syndrome: detection of carriers and prenatal diagnosis

We report the results of a molecular study of a large family segregating the complete form of the Androgen Insensitivity Syndrome (CAIS) in several family members from three generations. We identified the mutant allele by polymerase chain reaction (PCR) amplification of the short tandem repeat (CAG)n, highly polymorphic in the population, present in the first exon of the androgen receptor (AR) gene. In this family four different alleles were detected and one of these showed a perfect segregation with the disease.This study enabled us to identify the heterozygous females in this family. We think that this simple, indirect test, is also suitable for prenatal diagnosis of Morris' syndrome when the mother is heterozygous for the size of the short tandem repeat and one affected subject in the family may be studied.     

A Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome

BackgroundSwyer syndrome is a difference of sex development that is typically associated with mutations in genes responsible for testicular development. It is speculated that some cases may result from cryptic 45,X/46,XY mosaicism leading to abnormal gonadal development. The presence or absence of a 45,X lineage is important for prognosis and management.CaseWe present a case of apparent Swyer syndrome associated with a 46,XY chromosomal complement in lymphocytes and 45,X/46,XY mosaicism on analysis of her noncancerous gonad. Gonadal histology was consistent with a 45,X phenotype.Summary and ConclusionThis case demonstrates the clinical variability in the presentation of 45,X/46,XY mosaicism and highlights the importance of thorough genetic testing that includes consideration of chromosomal mosaicism. We will discuss the implications of this diagnosis for management.     

Dysgerminoma in a Prepubertal Girl with Complete 46XY Gonadal Dysgenesis: Case Report and Review of the Literature

BackgroundComplete 46XY gonadal dysgenesis (Swyer syndrome) is a rare and challenging diagnosis among prepubertal girls, as estrogen insufficiency becomes evident only during adolescence, with nonspecific symptoms such as primary amenorrhea and/or delayed puberty. Unfortunately, girls with Swyer syndrome are at high risk for malignancies in the dysgenetic gonads, which can be prevented only by performing prophylactic bilateral gonadectomy.CaseWe present a 9-year-old patient with Swyer syndrome diagnosed with dysgerminoma in the right gonad and gonadoblastoma in the left gonad after prophylactic bilateral gonadectomy.Summary and ConclusionConcerning the high risk of early gonadoblastoma and its malignant transformation, we recommend performing prophylactic bilateral gonadectomy at the time of diagnosis, even if the patient is prepubertal.     

Participant- and Clinician-Reported Long-Term Outcomes After Surgery in Individuals with Complete Androgen Insensitivity Syndrome

Study ObjectiveTo evaluate the outcomes of genital surgery through participant's and observer's satisfaction with the anatomical and functional result.Design and SettingMulticenter cross-sectional study in 14 clinics in 6 European countries in 2014-2015.ParticipantsSeventy-one individuals with complete androgen insensitivity syndrome (≥16 years old).InterventionsData from clinical report files, an optional gynecological examination, patient-reported outcomes on received surgical interventions, satisfaction with appearance and function after surgery, and effect of the surgical procedure on life.Main Outcome MeasuresOutcomes were calculated per different surgical treatments. Linear regression models were used for associations with vaginal satisfaction.ResultsSixty-three participants had received surgery: 62 gonadectomies, 12 vaginal surgeries with or without vaginal dilations, 9 vaginal dilations only, and 2 breast enlargements. More than half of the participants took part in the gynecological examination. Vaginal length was similar in those without (60 mm) and with (67 mm) vaginoplasty and/or vaginal dilations. Participant- and observer-reported appearance of the genitals were generally satisfactory to good. Sexual complaints (pain or bleeding during/after intercourse) were common. Vaginal satisfaction was strongly associated with satisfaction with sex life in general, whereas vaginal interventions and number of surgeries were not. Many participants reported a negative effect of gonadectomy on their life.ConclusionDespite good genital appearance, functional problems are commonly reported, across the different nonsurgical and surgical regimens. Patient-reported outcomes should be evaluated before and after surgical procedures. Because of the negative effect on life and the low risk of malignancy, gonadectomy should be deferred to adulthood with regular follow-up.