染色体核型与基因检测不符的性发育异常1例报道并文献复习  

Sex development disorder with discordant chromosome karyotype and gene detection:a case report and literature review

作　　者：任雁林[1] 李亚丽[2] 李坤[3] 张凡[3] 戎立敏[2] 余小平[2] 谷君[4] 康燕华[1] 贺英[1] Ren Yan-Lin;Li Ya-Li;Li Kun;Zhang Fan;Rong Li-Min;Yu Xiao-Ping;Gu Jun;Kang Yan-Hua;He Ying(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Reproductive Genetics,Hebei Provincial People's Hospital,Shijiazhuang,Hebei 050051,China;Department of Pathology,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Endocrinology,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China)

机构地区：[1]河北北方学院附属第一医院妇产科,河北张家口075000 [2]河北省人民医院生殖遗传科,河北石家庄050051 [3]河北北方学院附属第一医院病理科,河北张家口075000 [4]河北北方学院附属第一医院内分泌科,河北张家口075000

出　　处：《解放军医学杂志》2025年第1期50-56,共7页Medical Journal of Chinese People's Liberation Army

摘　　要：目的报道1例染色体核型与基因检测结果不符的性发育异常患者的诊治及验证过程,并进行文献复习,以提高对性发育异常嵌合状况的认识。方法患者,14岁,2020年4月3日因“原发性闭经”就诊于河北北方学院附属第一医院,为女性性征,经超声/磁共振探查性腺、性腺轴功能测定、染色体核型和分子基因检测,以及盆腔探查、恶变性腺切除、激素替代等诊疗,药物性月经来潮。诊疗中发现患者染色体核型分析与分子基因检测结果不符,遂行三胚层细胞分别取样,荧光原位杂交技术(FISH)检测各胚层细胞的性染色体,XY探针标记性腺病理切片探究Y染色体在性腺中的分布差异,并比较手术前后抗米勒管激素(AMH)水平的变化。检索万方、PubMed等数据库,汇总相关的队列研究文献,了解该疾病目前的研究现状。结果患者体内45,X与46,XY细胞系在不同胚层以及同一胚层发生的组织间的嵌合差异较大。外胚层来源的口腔颊黏膜细胞45,X占比为30.0%(6/20),中胚层来源的外周血淋巴细胞45,X占比为9.7%(11/114),内胚层来源的膀胱脱落细胞45,X占比为20.4%(22/108)。XY探针标记的性腺病理切片提示一个减Y的嵌合状态,其中附睾结构区45,X细胞系嵌合占50.0%,恶性区域“Y”含量正常。性腺切除后AMH由7.28 pmol/L降至<0.07 pmol/L。复习文献发现,45,X/46,XY患者表型谱复杂,多数有Turner综合征的特征,女性表型有发生性腺肿瘤的风险。结论诊断性发育异常的疑难病例行外周血核型检测时须尽量增加计数细胞和分析细胞的数目,并行多胚层细胞取样;“Y”嵌合率高的性腺在腹腔中更易恶变;检测AMH水平可鉴别含Y染色体性发育异常的隐睾和无睾状态。Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and

关 键 词：性发育异常 染色体嵌合型 性腺肿瘤 抗米勒管激素 嵌合 

分 类 号：R711.1[医药卫生—妇产科学] R394.1[医药卫生—临床医学]