Extending the phenotypes associated with DICER1 mutations

✍ Scribed by William D. Foulkes; Amin Bahubeshi; Nancy Hamel; Barbara Pasini; Sofia Asioli; Gareth Baynam; Catherine S. Choong; Adrian Charles; Richard P. Frieder; Megan K. Dishop; Nicole Graf; Mesiha Ekim; Dorothée Bouron-Dal Soglio; Jocelyne Arseneau; Robert H. Young; Nelly Sabbaghian; Archana Srivastava; Marc D. Tischkowitz; John R. Priest

• Book ID: 102261315
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 136 KB
• Volume: 32
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.21600

✦ Synopsis

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.