Supplementary Material for: KARYOTYPING OF LYMPHOCYTES AND EPITHELIAL CELLS OF DISTINCT EMBRYONIC ORIGIN DOESN’T HELP TO PREDICT THE TURNER SYNDROME FEATURES

Background: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. Objective: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin) and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. Design and Patients: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. Results: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% versus 70.0%; p<0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p<0.01), but the predictive power was insufficient. Conclusion: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.

背景：在特纳综合征（Turner syndrome, TS）中，荧光原位杂交（fluorescent in situ hybridization, FISH）核型分析可作为经典核型分析的替代方案。
目的：本研究旨在评估来源于淋巴细胞（中胚层来源）、颊黏膜细胞（外胚层来源）及舌后涂片样本（内胚层来源）的FISH核型分析的附加价值，以明确45,X细胞系比例及其对患者表型的影响。
设计与研究对象：本研究在四家大学附属医院开展，纳入153名既往确诊为TS的女孩及女性受试者，所有受试者均接受经典核型分析与三项FISH检测。通过每种检测方法测定45,X细胞系比例，并将其与主要表型体征进行关联分析。
结果：经典核型分析在153名受试者中检出77例（50%）45,X/46,XX嵌合体、52例（34%）45,X单体型，其余24例（16%）为其他核型。淋巴细胞来源的FISH验证了52例初始45,X单体型病例中的47例，其余4例被重新归类为45,X/46,XX嵌合体，1例为45,X/47,XYY嵌合体。淋巴细胞来源的FISH检测所得的45,X细胞系比例高于经典核型分析（中位数分别为86.4%与70.0%；p<0.001），而颊黏膜细胞或舌后涂片细胞来源的FISH检测结果与经典核型分析无显著差异。携带多项特征性表型体征的患者，其平均45,X细胞系比例高于无此类体征的患者（p<0.01），但该关联的预测效能不足。
结论：FISH分析验证了经典核型分析的结果，仅少数45,X单体型病例被重新归类为嵌合体。45,X细胞系比例无法对患者表型产生具有临床意义的预测价值。颊黏膜细胞或舌后上皮细胞的FISH分析，可作为经典核型分析的非劣效、侵入性更低的替代方案。