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Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy
As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252268/ https://www.ncbi.nlm.nih.gov/pubmed/37296576 http://dx.doi.org/10.3390/cells12111455 |
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author | Sono, Reiri Larrinaga, Tania M. Huang, Alden Makhlouf, Frank Kang, Xuedong Su, Jonathan Lau, Ryan Arboleda, Valerie A. Biniwale, Reshma Fishbein, Gregory A. Khanlou, Negar Si, Ming-Sing Satou, Gary M. Halnon, Nancy Van Arsdell, Glen S. Gregorio, Carol C. Nelson, Stanly Touma, Marlin |
author_facet | Sono, Reiri Larrinaga, Tania M. Huang, Alden Makhlouf, Frank Kang, Xuedong Su, Jonathan Lau, Ryan Arboleda, Valerie A. Biniwale, Reshma Fishbein, Gregory A. Khanlou, Negar Si, Ming-Sing Satou, Gary M. Halnon, Nancy Van Arsdell, Glen S. Gregorio, Carol C. Nelson, Stanly Touma, Marlin |
author_sort | Sono, Reiri |
collection | PubMed |
description | As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2-related cardiomyopathy. |
format | Online Article Text |
id | pubmed-10252268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102522682023-06-10 Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy Sono, Reiri Larrinaga, Tania M. Huang, Alden Makhlouf, Frank Kang, Xuedong Su, Jonathan Lau, Ryan Arboleda, Valerie A. Biniwale, Reshma Fishbein, Gregory A. Khanlou, Negar Si, Ming-Sing Satou, Gary M. Halnon, Nancy Van Arsdell, Glen S. Gregorio, Carol C. Nelson, Stanly Touma, Marlin Cells Article As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2-related cardiomyopathy. MDPI 2023-05-23 /pmc/articles/PMC10252268/ /pubmed/37296576 http://dx.doi.org/10.3390/cells12111455 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sono, Reiri Larrinaga, Tania M. Huang, Alden Makhlouf, Frank Kang, Xuedong Su, Jonathan Lau, Ryan Arboleda, Valerie A. Biniwale, Reshma Fishbein, Gregory A. Khanlou, Negar Si, Ming-Sing Satou, Gary M. Halnon, Nancy Van Arsdell, Glen S. Gregorio, Carol C. Nelson, Stanly Touma, Marlin Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title | Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title_full | Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title_fullStr | Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title_full_unstemmed | Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title_short | Whole-Exome Sequencing Identifies Homozygote Nonsense Variants in LMOD2 Gene Causing Infantile Dilated Cardiomyopathy |
title_sort | whole-exome sequencing identifies homozygote nonsense variants in lmod2 gene causing infantile dilated cardiomyopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252268/ https://www.ncbi.nlm.nih.gov/pubmed/37296576 http://dx.doi.org/10.3390/cells12111455 |
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