Service de Génétique, Institut Curie, Paris, France.
Unité Clinique d'Oncologie génétique, Centre Léon Bérard, Lyon, France.
Pediatr Blood Cancer. 2018 Jun;65(6):e27005. doi: 10.1002/pbc.27005. Epub 2018 Feb 22.
Germline DICER1 pathogenic variants predispose to numerous benign and malignant tumors. In this report, we describe DICER1 gene analysis in an adolescent diagnosed with multinodular goiter, ovarian Sertoli-Leydig cell tumor, and lung cyst. DICER1 mutational screening at the DNA level failed to detect any pathogenic variant. Subsequent messenger RNA (mRNA) analysis revealed a 132 nucleotide intronic sequence exonization. This truncating event was caused by a deep intronic mutation generating a de novo acceptor splice site. This study demonstrates that some undetected DICER1 mutations should be investigated at the mRNA level.
胚系 DICER1 致病性变异可导致多种良性和恶性肿瘤。在本报告中，我们描述了一名青少年患有多发性结节性甲状腺肿、卵巢 Sertoli-Leydig 细胞瘤和肺囊肿，对 DICER1 基因进行了分析。在 DNA 水平上进行 DICER1 突变筛查未能发现任何致病性变异。随后的信使 RNA（mRNA）分析显示 132 个核苷酸内含子序列外显子化。这种截断事件是由深内含子突变产生的新的供体位点剪接引起的。本研究表明，一些未检测到的 DICER1 突变应在 mRNA 水平进行研究。
