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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doaj-b0c6455175fb4eb4ad07ba3acdbf8b8d2020-11-25T04:09:40ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-11-01710.3389/fcvm.2020.582350582350A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese PatientZhuang-Zhuang Yuan0Zhuang-Zhuang Yuan1Zhuang-Zhuang Yuan2Liang-Liang Fan3Liang-Liang Fan4Zi-Chen Jiang5Yi-Feng Yang6Zhi-Ping Tan7Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, ChinaUniversity of California, San Diego, San Diego, CA, United StatesClinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaClinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fcvm.2020.582350/fullcongenital heart defect (CHD)whole exome sequencingstopgain variantdextrocardiaMMP21 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Liang-Liang Fan Liang-Liang Fan Zi-Chen Jiang Yi-Feng Yang Zhi-Ping Tan |
spellingShingle |
Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Liang-Liang Fan Liang-Liang Fan Zi-Chen Jiang Yi-Feng Yang Zhi-Ping Tan A Novel Nonsense MMP21 Variant Causes Dextrocardia and Congenital Heart Disease in a Han Chinese Patient Frontiers in Cardiovascular Medicine congenital heart defect (CHD) whole exome sequencing stopgain variant dextrocardia MMP21 |
author_facet |
Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Zhuang-Zhuang Yuan Liang-Liang Fan Liang-Liang Fan Zi-Chen Jiang Yi-Feng Yang Zhi-Ping Tan |
author_sort |
Zhuang-Zhuang Yuan |
title |
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_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_sort |
novel nonsense mmp21 variant causes dextrocardia and congenital heart disease in a han chinese patient |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2020-11-01 |
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. |
topic |
congenital heart defect (CHD) whole exome sequencing stopgain variant dextrocardia MMP21 |
url |
https://www.frontiersin.org/articles/10.3389/fcvm.2020.582350/full |
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