四配子异源嵌合体导致的真两性畸形机制研究

目的 :报告 1例四配子异源嵌合体导致的真两性畸形并讨论其发病机制。　方法 :对 1例外生殖器模糊的患者外周血的淋巴细胞、经培养的皮肤成纤维细胞、两种不同性腺组织的成纤维细胞进行染色体核型分析 ,同时用X和Y染色体探针进行双色荧光原位杂交 (FISH) ;对患者红细胞血型、人类白细胞抗原 (HLA)和 77个短重复序列 (STR)微卫星标记进行检测 ;对患者性腺的 2种不同组织进行组织病理学检查 ;同时对患者的父母进行红细胞血型、HLA和STR检测。　结果 :患者外周血淋巴细胞、皮肤成纤维细胞、呈白色和黄色性腺组织的成纤维细胞染色体核型均为 4 6 ,XX/ 4 6 ,XY ;FISH检测所有细胞都显示了XX或XY的杂交信号。 4 6 ,XY的核型在外周血淋巴细胞、皮肤成纤维细胞和白色性腺组织的成纤维细胞中占优势 ;4 6 ,XX的核型在黄色性腺组织的成纤维细胞中占优势。外周血淋巴细胞及 3种不同组织培养物的STR位点检测、ABO血型分析和HLA检测都显示有 2个不同的单倍体来自父亲 ,1个单倍体来自母亲。组织病理学检查患者同一性腺上有两种不同组织 ,呈白色的组织是睾丸 ,呈黄色的组织是卵巢。　结论 :性腺组织病理学检查、染色体核型分析、FISH是鉴定真两性畸形患者的有效方法 ,红细胞血型、HLA和STR可为鉴定四配子异源嵌合体提供?

The Mechanism of Tetragametic Chimerism in a True Hermaphroditism with 46,XX/46,XY

Objective: To report a true hermaphroditism due to a teragametic chimerism and to discuss the pathogenesis of tetragametic chimerism. Methods: Chromosomal analysis and fluorescence in situ hybridization(FISH) were carried out on the lymphocytes from the blood and on the fibroblasts from the cultured skin and on fibroblasfs from two different kinds of gonadal tissues of the patient with ambiguous genitalia respectively. Blood groups, human leukocyte antigen (HLA) haplotyping and 77 short tandem repeat (STR) microsatellite markers were tested. The two kinds of tissues in the gonad were detected by histopathological examination. Blood groups, HLA haplotyping and 77 STR microsatellite markers parents of the patient's were also analyzed. Results: Either 46,XX or 46,XY karyotype was found in the lymphocytes of the blood and in the fibroblasts of the cultured skin and of the two different kinds of gonadal tissues. Two X chromosome-specific signals or one X and one Y signal were detected in each interphase nucleus by FISH from the lymphocytes of the blood and the fibroblasts of three different tissue cultures. The karyotype of the 46,XY cell line predominated in all cultures except the cultured-fibroblasts from yellow gonadal tissues. STR marker analysis, ABO grouping and HLA study from the patient were identified a single haplotype in the patient from the mother and two different haplotypes from the father. Two kinds of tissues in the gonad were observed by histopathological examination. The yellow tissue was ovary and the white one was testis. Conclusions: Histopathological examination and chromosomal analysis combined with FISH are very useful methods for the diagnosis of true hermaphroditism. Blood typing, HLA and short tandem repeat microsatellite markers afford strong evidence for confirming tetragametic chimerism. The mechanism of tetragametic chimerism in true hermaphroditism can be explained by a parthenogenetic division of a haploid nucleu into two identical gametes, followed by fertilization with both X and Y spermatozoa and then developed into an organism.