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Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections

Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic c...

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Autores principales: Kuang, Shao-Qing, Guo, Dong-Chuan, Prakash, Siddharth K., McDonald, Merry-Lynn N., Johnson, Ralph J., Wang, Min, Regalado, Ellen S., Russell, Ludivine, Cao, Jiu-Mei, Kwartler, Callie, Fraivillig, Kurt, Coselli, Joseph S., Safi, Hazim J., Estrera, Anthony L., Leal, Suzanne M., LeMaire, Scott A., Belmont, John W., Milewicz, Dianna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116911/
https://www.ncbi.nlm.nih.gov/pubmed/21698135
http://dx.doi.org/10.1371/journal.pgen.1002118
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author Kuang, Shao-Qing
Guo, Dong-Chuan
Prakash, Siddharth K.
McDonald, Merry-Lynn N.
Johnson, Ralph J.
Wang, Min
Regalado, Ellen S.
Russell, Ludivine
Cao, Jiu-Mei
Kwartler, Callie
Fraivillig, Kurt
Coselli, Joseph S.
Safi, Hazim J.
Estrera, Anthony L.
Leal, Suzanne M.
LeMaire, Scott A.
Belmont, John W.
Milewicz, Dianna M.
author_facet Kuang, Shao-Qing
Guo, Dong-Chuan
Prakash, Siddharth K.
McDonald, Merry-Lynn N.
Johnson, Ralph J.
Wang, Min
Regalado, Ellen S.
Russell, Ludivine
Cao, Jiu-Mei
Kwartler, Callie
Fraivillig, Kurt
Coselli, Joseph S.
Safi, Hazim J.
Estrera, Anthony L.
Leal, Suzanne M.
LeMaire, Scott A.
Belmont, John W.
Milewicz, Dianna M.
author_sort Kuang, Shao-Qing
collection PubMed
description Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10(−5), OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes.
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spelling pubmed-31169112011-06-22 Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections Kuang, Shao-Qing Guo, Dong-Chuan Prakash, Siddharth K. McDonald, Merry-Lynn N. Johnson, Ralph J. Wang, Min Regalado, Ellen S. Russell, Ludivine Cao, Jiu-Mei Kwartler, Callie Fraivillig, Kurt Coselli, Joseph S. Safi, Hazim J. Estrera, Anthony L. Leal, Suzanne M. LeMaire, Scott A. Belmont, John W. Milewicz, Dianna M. PLoS Genet Research Article Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10(−5), OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes. Public Library of Science 2011-06-16 /pmc/articles/PMC3116911/ /pubmed/21698135 http://dx.doi.org/10.1371/journal.pgen.1002118 Text en Kuang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kuang, Shao-Qing
Guo, Dong-Chuan
Prakash, Siddharth K.
McDonald, Merry-Lynn N.
Johnson, Ralph J.
Wang, Min
Regalado, Ellen S.
Russell, Ludivine
Cao, Jiu-Mei
Kwartler, Callie
Fraivillig, Kurt
Coselli, Joseph S.
Safi, Hazim J.
Estrera, Anthony L.
Leal, Suzanne M.
LeMaire, Scott A.
Belmont, John W.
Milewicz, Dianna M.
Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title_full Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title_fullStr Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title_full_unstemmed Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title_short Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections
title_sort recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116911/
https://www.ncbi.nlm.nih.gov/pubmed/21698135
http://dx.doi.org/10.1371/journal.pgen.1002118
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