Open AccessA Genome-First Approach to Characterize DICER1 Pathogenic Variant Prevalence, Penetrance, and Phenotype
Author(s) -
Uyenlinh L. Mirshahi,
Jung Kim,
Ana F. Best,
Zongming E. Chen,
Ying Hu,
Jeremy S. Haley,
Alicia Golden,
Richard C. Stahl,
Kandamurugu Manickam,
Ann G. Carr,
Laura A. Harney,
Amanda Field,
Jessica N. Hatton,
Kris Ann P. Schultz,
Andrew J. Bauer,
D. Ashley Hill,
Philip S. Rosenberg,
Michael F. Murray,
David J. Carey,
Douglas R. Stewart
Publication year - 2021
Publication title -
jama network open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.278
H-Index - 39
ISSN - 2574-3805
DOI - 10.1001/jamanetworkopen.2021.0112
Subject(s) - penetrance , germline , medicine , germline mutation , cohort , thyroid cancer , exome sequencing , genetics , exome , cancer , phenotype , oncology , mutation , biology , gene
Key Points Question What are the prevalence, risk, and phenotypic spectrum of individuals with a germline putative loss-of-function (pLOF) variant in DICER1 according to a genome-first approach in a population-scale cohort? Findings In this cohort study, DICER1 pLOF variants were more than twice as common (even after adjustment for relatedness) than previously observed. Malignant tumors were observed in 16% of participants with a DICER1 pLOF variant, which is comparable to the frequency of neoplasms in the largest phenotype-first DICER1 studies published to date. Meaning The genome-first approach complements more traditional approaches to syndrome delineation and may be an efficient approach for risk estimation in monogenic disorders.
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