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A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient

The position and morphology of human internal organs are asymmetrically distributed along the left–right axis. Aberrant left–right patterning in the developing embryo can lead to a series of congenital laterality defects, such as dextrocardia and heterotaxy syndrome. Laterality defects are a genetic...

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Autores principales: Yuan, Zhuang-Zhuang, Fan, Liang-Liang, Jiang, Zi-Chen, Yang, Yi-Feng, Tan, Zhi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680847/
https://www.ncbi.nlm.nih.gov/pubmed/33240936
http://dx.doi.org/10.3389/fcvm.2020.582350
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author Yuan, Zhuang-Zhuang
Fan, Liang-Liang
Jiang, Zi-Chen
Yang, Yi-Feng
Tan, Zhi-Ping
author_facet Yuan, Zhuang-Zhuang
Fan, Liang-Liang
Jiang, Zi-Chen
Yang, Yi-Feng
Tan, Zhi-Ping
author_sort Yuan, Zhuang-Zhuang
collection PubMed
description The position and morphology of human internal organs are asymmetrically distributed along the left–right axis. Aberrant left–right patterning in the developing embryo can lead to a series of congenital laterality defects, such as dextrocardia and heterotaxy syndrome. Laterality defects are a genetic condition; however, pathogenic genetic lesions are found in only one-fifth of patients. In this study, whole-exome sequencing was conducted for 78 patients with laterality defects. We identified a novel stopgain variant in MMP21 (c.G496T; p.G166(*)) in a Chinese patient with mirror-image dextrocardia. This variant caused a truncated MMP21 mRNA containing only the signal peptide and propeptide, while the coding sequence of matrix metalloproteinase-21 was almost entirely absent. To the best of our knowledge, this novel variant is the first homozygous stopgain variant identified in dextrocardia patients, and the first MMP21 variant found in East Asia. Our findings expand the spectrum of MMP21 variants and provide support for the critical role of MMP21 during left–right patterning in the Han Chinese population.
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spelling pubmed-76808472020-11-24 A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient Yuan, Zhuang-Zhuang Fan, Liang-Liang Jiang, Zi-Chen Yang, Yi-Feng Tan, Zhi-Ping Front Cardiovasc Med Cardiovascular Medicine The position and morphology of human internal organs are asymmetrically distributed along the left–right axis. Aberrant left–right patterning in the developing embryo can lead to a series of congenital laterality defects, such as dextrocardia and heterotaxy syndrome. Laterality defects are a genetic condition; however, pathogenic genetic lesions are found in only one-fifth of patients. In this study, whole-exome sequencing was conducted for 78 patients with laterality defects. We identified a novel stopgain variant in MMP21 (c.G496T; p.G166(*)) in a Chinese patient with mirror-image dextrocardia. This variant caused a truncated MMP21 mRNA containing only the signal peptide and propeptide, while the coding sequence of matrix metalloproteinase-21 was almost entirely absent. To the best of our knowledge, this novel variant is the first homozygous stopgain variant identified in dextrocardia patients, and the first MMP21 variant found in East Asia. Our findings expand the spectrum of MMP21 variants and provide support for the critical role of MMP21 during left–right patterning in the Han Chinese population. Frontiers Media S.A. 2020-11-09 /pmc/articles/PMC7680847/ /pubmed/33240936 http://dx.doi.org/10.3389/fcvm.2020.582350 Text en Copyright © 2020 Yuan, Fan, Jiang, Yang and Tan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Yuan, Zhuang-Zhuang
Fan, Liang-Liang
Jiang, Zi-Chen
Yang, Yi-Feng
Tan, Zhi-Ping
A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title_full A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title_fullStr A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title_full_unstemmed A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title_short A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient
title_sort novel nonsense mmp21 variant causes dextrocardia and congenital heart disease in a han chinese patient
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680847/
https://www.ncbi.nlm.nih.gov/pubmed/33240936
http://dx.doi.org/10.3389/fcvm.2020.582350
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