Affordable Access

deepdyve-link
Publisher Website

Identification of two 14q32 deletions involving DICER1 associated with the development of DICER1-related tumors.

Authors
  • Herriges, John C1
  • Brown, Sara2
  • Longhurst, Maria2
  • Ozmore, Jillian3
  • Moeschler, John B4
  • Janze, Aura5
  • Meck, Jeanne5
  • South, Sarah T6
  • Andersen, Erica F6
  • 1 Department of Pathology, University of Utah, Salt Lake City, UT, United States; Cytogenetics and Genomic Microarray, ARUP Laboratories, Salt Lake City, UT, United States. Electronic address: [email protected] , (United States)
  • 2 Cytogenetics and Genomic Microarray, ARUP Laboratories, Salt Lake City, UT, United States. , (United States)
  • 3 Medical Genetics, Children's Hospital at Dartmouth, NH, Lebanon. , (Lebanon)
  • 4 Geisel School of Medicine, Dartmouth College, Hanover, NH, United States. , (United States)
  • 5 GeneDx, Gaithersburg, MD, United States. , (United States)
  • 6 Department of Pathology, University of Utah, Salt Lake City, UT, United States; Cytogenetics and Genomic Microarray, ARUP Laboratories, Salt Lake City, UT, United States. , (United States)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Apr 24, 2018
Identifiers
DOI: 10.1016/j.ejmg.2018.04.011
PMID: 29698806
Source
Medline
Keywords
License
Unknown

Abstract

DICER1 encodes an RNase III endonuclease protein that regulates the production of small non-coding RNAs. Germline mutations in DICER1 are associated with an autosomal dominant hereditary cancer predisposition syndrome that confers an increased risk for the development of several rare childhood and adult-onset tumors, the most frequent of which include pleuropulmonary blastoma, ovarian sex cord-stromal tumors, cystic nephroma, and thyroid gland neoplasia. The majority of reported germline DICER1 mutations are truncating sequence-level alterations, suggesting that a loss-of-function type mechanism drives tumor formation in DICER1 syndrome. However, reports of patients with germline DICER1 whole gene deletions are limited, and thus far, only two have reported an association with tumor development. Here we report the clinical findings of three patients from two unrelated families with 14q32 deletions that encompass the DICER1 locus. The deletion identified in Family I is 1.4 Mb and was initially identified in a 6-year-old male referred for developmental delay, hypotonia, macrocephaly, obesity, and behavioral problems. Subsequent testing revealed that this deletion was inherited from his mother, who had a clinical history that included bilateral multinodular goiter and papillary thyroid carcinoma. The second deletion is 5.0 Mb and was identified in a 15-year-old female who presented with autism, coarse facial features, Sertoli-Leydig cell tumor, and Wilms' tumor. These findings provide additional supportive evidence that germline deletion of DICER1 confers an increased risk for DICER1-related tumor development, and provide new insight into the clinical significance of deletions involving the 14q32 region.

Report this publication

Statistics

Seen <100 times