title: Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.
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.
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.forename: Gilles
authors.initials: G
authors.lastname: Maussion
authors.forename: Liam
authors.initials: L
authors.lastname: Crapper
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Ian
authors.initials: I
authors.lastname: Blumenthal
authors.forename: Carrie
authors.initials: C
authors.lastname: Hanscom
authors.forename: Colby
authors.initials: C
authors.lastname: Chiang
authors.forename: Amelia
authors.initials: A
authors.lastname: Lindgren
authors.forename: Shahrin
authors.initials: S
authors.lastname: Pereira
authors.forename: Douglas
authors.initials: D
authors.lastname: Ruderfer
authors.forename: Alpha B
authors.initials: AB
authors.lastname: Diallo
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Chen
authors.forename: Carolina
authors.initials: C
authors.lastname: Gigek
authors.forename: David J
authors.initials: DJ
authors.lastname: Harris
authors.forename: Va
authors.initials: V
authors.lastname: Lip
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Marta
authors.initials: M
authors.lastname: Biagioli
authors.forename: Marcy E
authors.initials: ME
authors.lastname: Macdonald
authors.forename: Michael
authors.initials: M
authors.lastname: Lin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haggarty
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Stuart
authors.initials: S
authors.lastname: Schwartz
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Marvin R
authors.initials: MR
authors.lastname: Natowicz
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Carl
authors.initials: C
authors.lastname: Ernst
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing; D001483:Base Sequence; D056905:Chromosome Breakpoints; D002880:Chromosomes, Human, Pair 11; D002889:Chromosomes, Human, Pair 2; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D023061:Gene Order; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D062085:RNA, Long Noncoding