Extending the phenotypes associated with DICER1 mutations
Extending the phenotypes associated with DICER1 mutations
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DOI：
10.1002/humu.21600
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发表时间：
2011-12-01
期刊：
影响因子：
3.9
通讯作者：
Priest, John R.
中科院分区：
文献类型：
--
作者：
Foulkes, William D.;Bahubeshi, Amin;Priest, John R.
DICER 1对胚胎发生和早期发育至关重要。在全球范围内，42例先证者报告了40种不同的杂合子生殖系DICER 1突变，这些先证者在儿童或年轻人时发生胸膜肺母细胞瘤（PPB）、囊性肾瘤（CN）、卵巢性索间质肿瘤（尤其是Sertoli-Leydig细胞瘤[SLCT]）和/或多结节性甲状腺肿（MNG）。我们报告了另外7个家族的DICER 1突变，这些家族表现为子宫颈胚胎性横纹肌肉瘤（cERMS，4例）和原始神经外胚层肿瘤（cPNET，1例），肾母细胞瘤（WT，3例），肺隔离症（PS，1例）和幼年肠息肉（1例）。一名携带者（年龄25岁）发生了大腿多形性肉瘤;另一名携带者发生了大动脉转位（TGA）。这些观察结果表明，cERMS、cPNET、WT、PS和幼年性息肉属于DICER 1相关疾病的范围。DICER 1似乎是与cERMS、cPNET和PS病因学有关的第一个基因。青年肉瘤和先天性畸形（如TGA）也可能与此相关。32：13811384，2011. (C)2011 Wiley Periodicals，Inc.
DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1 mutations in seven additional families that manifested uterine cervix embryonal rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET, one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case), and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a pleomorphic sarcoma of the thigh; another carrier had transposition of great arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be the first gene implicated in the etiology of cERMS, cPNET, and PS. Young adulthood sarcomas and perhaps congenital malformations such as TGA may also be associated. 32:13811384, 2011. (C) 2011 Wiley Periodicals, Inc.