Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Am J Hum Genet. 2012 Dec 7;91(6):1128-34. doi: 10.1016/j.ajhg.2012.10.016.
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.
长链非编码 RNA（lincRNA）是一类新发现的 RNA，其在人类疾病中的重要性尚未确定。我们发现了一名严重发育迟缓的 16 岁女性，其核型为 46,XX,t(2;11)(p25.1;p15.1)dn，不存在临床显著的拷贝数变异（CNV）。通过捕获 DNA 并对易位断点进行下一代测序，发现 2 号染色体上的单个非编码基因 LINC00299 受到破坏，该基因的 RNA 产物在所有测量的组织中均有表达，但在大脑中表达最为丰富。在一系列因临床诊断测试而转诊的其他无关受试者中，我们发现有 4 名受试者存在与神经发育异常相关的外显子跨越缺失，影响了该基因座。在近 14000 名对照受试者中未发现 LINC00299 编码序列的破坏。这些 LINC00299 受到破坏的受试者提示，特定的非编码 RNA 参与了大脑发育，并提出了这样一种可能性，即作为一类，lincRNA 的异常可能在人类发育障碍中发挥重要作用。
