A Balanced Reciprocal Translocation T(2;9)(p25;q13) Disrupting the Gene in a Patient with Intellectual Disability

Overview

Journal Mol Syndromol

Date 2019 Oct 12

PMID 31602198

Citations 1

Authors

Halinna Dornelles-Wawruk

Romina Soledad Heredia

Milton R de Paula-Junior

Maria Terezinha O Cardoso

Raphael S Bonadio

Bianca F Dos Reis

Aline Pic-Taylor

Silviene F De Oliveira

Juliana F Mazzeu

Affiliations

Soon will be listed here.

Abstract

Long intergenic noncoding RNAs (lincRNAs) are a class of noncoding RNAs implicated in several biological processes. LincRNA 299 () maps to 2p25.1 and its function is still unknown. However, this gene has been proposed as a candidate for intellectual disability (ID) in a patient with a balanced translocation where the breakpoint disrupted its ORF. Here, we describe a new case of disruption associated with ID. The individual, a 42-year-old woman, was referred to the clinical geneticist because of her son who had severe syndromic ID. G-banding and chromosomal microarray analysis were performed. Karyotyping of the boy revealed an extranumerary derivative chromosome identified as an unbalanced translocation between chromosomes 2 and 9 of maternal origin. The mother's karyotype showed a balanced translocation 46,XX,t(2;9)(p25;q13). Chromosomal microarray indicated a disruption of . These data corroborate the role of as a causative gene for ID and broadens the spectrum of -related phenotypes.

Citing Articles

Interpreting the impact of noncoding structural variation in neurodevelopmental disorders.

Dhaene E, Vergult S Genet Med. 2020; 23(1):34-46.

PMID: 32973355 PMC: 7790743. DOI: 10.1038/s41436-020-00974-1.

References

Talkowski M, Maussion G, Crapper L, Rosenfeld J, Blumenthal I, Hanscom C . Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities. Am J Hum Genet. 2012; 91(6):1128-34. PMC: 3516594. DOI: 10.1016/j.ajhg.2012.10.016. View

Petruk S, Sedkov Y, Riley K, Hodgson J, Schweisguth F, Hirose S . Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell. 2006; 127(6):1209-21. PMC: 1866366. DOI: 10.1016/j.cell.2006.10.039. View

Liu Y, Chen Y, Tan L, Zhao H, Xiao N . Linc00299/miR-490-3p/AURKA axis regulates cell growth and migration in atherosclerosis. Heart Vessels. 2019; 34(8):1370-1380. DOI: 10.1007/s00380-019-01356-7. View

Currall B, Chiang C, Talkowski M, Morton C . Mechanisms for Structural Variation in the Human Genome. Curr Genet Med Rep. 2013; 1(2):81-90. PMC: 3665418. DOI: 10.1007/s40142-013-0012-8. View

Brown C, Hendrich B, Rupert J, Lafreniere R, Xing Y, Lawrence J . The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992; 71(3):527-42. DOI: 10.1016/0092-8674(92)90520-m. View

Sun M, Kraus W . From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease. Endocr Rev. 2014; 36(1):25-64. PMC: 4309736. DOI: 10.1210/er.2014-1034. View

Blake J, Riddell A, Theiss S, Gonzalez A, Haase B, Jauch A . Sequencing of a patient with balanced chromosome abnormalities and neurodevelopmental disease identifies disruption of multiple high risk loci by structural variation. PLoS One. 2014; 9(3):e90894. PMC: 3953210. DOI: 10.1371/journal.pone.0090894. View

Hou J, Long H, Zhou C, Zheng S, Wu H, Guo T . Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro. Stem Cell Res Ther. 2017; 8(1):4. PMC: 5242041. DOI: 10.1186/s13287-016-0454-5. View

Derrien T, Guigo R, Johnson R . The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter". Front Genet. 2012; 2:107. PMC: 3266617. DOI: 10.3389/fgene.2011.00107. View

10.

Wang H, Li W, Guo R, Sun J, Cui J, Wang G . An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies. Int J Cancer. 2014; 135(12):2783-94. DOI: 10.1002/ijc.28922. View

11.

Liu S, Mitra R, Zhao M, Fan W, Eischen C, Yin F . The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development. Mol Cancer Ther. 2016; 15(12):2977-2986. PMC: 5136321. DOI: 10.1158/1535-7163.MCT-16-0320. View

12.

Kurihara M, Shiraishi A, Satake H, Kimura A . A conserved noncoding sequence can function as a spermatocyte-specific enhancer and a bidirectional promoter for a ubiquitously expressed gene and a testis-specific long noncoding RNA. J Mol Biol. 2014; 426(17):3069-93. DOI: 10.1016/j.jmb.2014.06.018. View

13.

Hou J, Zhou C, Long H, Zheng S, Guo T, Wu Q . Long noncoding RNAs: Novel molecules in cardiovascular biology, disease and regeneration. Exp Mol Pathol. 2016; 100(3):493-501. DOI: 10.1016/j.yexmp.2016.05.006. View

14.

Bhan A, Mandal S . Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 2014; 9(9):1932-56. DOI: 10.1002/cmdc.201300534. View

15.

Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider P . MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003; 22(39):8031-41. DOI: 10.1038/sj.onc.1206928. View

16.

Bermejo J, Huang G, Manoochehri M, Mesa K, Schick M, Silos R . Long intergenic noncoding RNA 299 methylation in peripheral blood is a biomarker for triple-negative breast cancer. Epigenomics. 2018; 11(1):81-93. DOI: 10.2217/epi-2018-0121. View