Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.

Am J Hum Genet
Authors
Keywords
Abstract

Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.

Year of Publication
2012
Journal
Am J Hum Genet
Volume
91
Issue
6
Pages
1128-34
Date Published
2012 Dec 07
ISSN
1537-6605
URL
DOI
10.1016/j.ajhg.2012.10.016
PubMed ID
23217328
PubMed Central ID
PMC3516594
Links
Grant list
HD065286 / HD / NICHD NIH HHS / United States
GM061354 / GM / NIGMS NIH HHS / United States
K99MH095867 / MH / NIMH NIH HHS / United States
K99 MH095867 / MH / NIMH NIH HHS / United States
R33 MH087896 / MH / NIMH NIH HHS / United States
R33MH087896 / MH / NIMH NIH HHS / United States
P01 GM061354 / GM / NIGMS NIH HHS / United States
R21 HD065286 / HD / NICHD NIH HHS / United States