Freriks Kim, Timmers Henri J L M, Netea-Maier Romana T, Beerendonk Catharina C M, Otten Barto J, van Alfen-van der Velden Janiëlle A E M, Traas Maaike A F, Mieloo Hanneke, van de Zande Guillaume W H J F L, Hoefsloot Lies H, Hermus Ad R M M, Smeets Dominique F C M
Department of Internal Medicine, Division of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Med Genet. 2013 Sep;56(9):497-501. doi: 10.1016/j.ejmg.2013.07.008. Epub 2013 Aug 9.
Turner syndrome (TS) is the result of (partial) X chromosome monosomy. In general, the diagnosis is based on karyotyping of 30 blood lymphocytes. This technique, however, does not rule out tissue mosaicism or low grade mosaicism in the blood. Because of the associated risk of gonadoblastoma, mosaicism is especially important in case this involves a Y chromosome. We investigated different approaches to improve the detection of mosaicisms in 162 adult women with TS (mean age 29.9 ± 10.3). Standard karyotyping identified 75 patients (46.3%) with a non-mosaic monosomy 45,X. Of these 75 patients, 63 underwent additional investigations including FISH on buccal cells with X- and Y-specific probes and PCR-Y on blood. FISH analysis of buccal cells revealed a mosaicism in 19 of the 63 patients (30.2%). In five patients the additional cell lines contained a (derivative) Y chromosome. With sensitive real-time PCR we confirmed the presence of this Y chromosome in blood in three of the five cases. Although Y chromosome material was established in ovarian tissue in two patients, no gonadoblastoma was found. Our results confirm the notion that TS patients with 45,X on conventional karyotyping often have tissue specific mosaicisms, some of which include a Y chromosome. Although further investigations are needed to estimate the risk of gonadoblastoma in patients with Y chromosome material in buccal cells, we conclude that FISH or real-time PCR on buccal cells should be considered in TS patients with 45,X on standard karyotyping.
特纳综合征（TS）是（部分）X染色体单体性的结果。一般来说，诊断基于对30个血液淋巴细胞进行核型分析。然而，这项技术并不能排除组织嵌合现象或血液中的低水平嵌合现象。由于存在性腺母细胞瘤的相关风险，嵌合现象在涉及Y染色体时尤为重要。我们研究了不同方法以提高对162名成年TS女性（平均年龄29.9±10.3岁）中嵌合现象的检测。标准核型分析确定了75名患者（46.3%）为非嵌合性45,X单体性。在这75名患者中，63名接受了额外检查，包括使用X和Y特异性探针进行颊黏膜细胞荧光原位杂交（FISH）以及血液的PCR-Y检测。颊黏膜细胞的FISH分析显示，63名患者中有19名（30.2%）存在嵌合现象。在5名患者中，额外的细胞系含有（衍生的）Y染色体。通过灵敏的实时PCR，我们在5例中的3例中证实了血液中存在这条Y染色体。尽管在2例患者的卵巢组织中发现了Y染色体物质，但未发现性腺母细胞瘤。我们的结果证实了这样一种观点，即传统核型分析显示为45,X的TS患者通常存在组织特异性嵌合现象，其中一些包括Y染色体。尽管需要进一步研究来评估颊黏膜细胞中存在Y染色体物质的患者发生性腺母细胞瘤的风险，但我们得出结论，对于标准核型分析为45,X的TS患者，应考虑对颊黏膜细胞进行FISH或实时PCR检测。
