DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls.

DICER1 综合征是一种遗传性疾病，与多种器官发生错构瘤和肿瘤病变的风险增加相关，主要是在早期。DICER1的种系致病性变异会导致这种情况。检测DICER1中意义不确定的变异或发现不常见的表型会使诊断复杂化，并可能对患者护理产生负面影响。我们介绍了两名疑似患有 DICER1 综合征的无关患者。两名女性（年龄分别为 13 岁和 15 岁）均患有多结节性甲状腺肿（甲状腺滤泡结节病）和卵巢肿瘤。一名被诊断患有卵巢支持间质细胞瘤 (SLCT)，另一名被诊断患有卵巢幼年颗粒细胞瘤，后来被重新分类为 SLCT 的网状变体。基因筛查显示DICER1没有种系致病变异。然而，发现了两个潜在的剪接变体，DICER1 c.5365-4A>G 和 c.5527+3A>G。此外，在甲状腺和卵巢组织中检测到典型的体细胞DICER1 RNase IIIb 热点突变。计算机剪接算法预测了两种种系变体的剪接改变，并且通过两种变体的 RNA 测定证实了外显子 25 的跳跃。卵巢肿瘤的重新分类、导致对 DICER1 综合征相关性的认识以及种系内含子变异的表征均应用于最近描述的DICER1变异分类规则。最终证实这两名少女患有 DICER1 综合征。