Your browser doesn't support javascript.
loading
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.
Afiliação
  • Sono R; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Larrinaga TM; Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ 85721, USA.
  • Huang A; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Makhlouf F; Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Kang X; Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Su J; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Lau R; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Arboleda VA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Biniwale R; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Fishbein GA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
  • Khanlou N; Eli and Edyth Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA.
  • Si MS; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Satou GM; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Halnon N; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Ucla Congenital Heart Defects-BioCore Faculty; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Van Arsdell GS; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Gregorio CC; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Nelson S; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Touma M; Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Cells ; 12(11)2023 05 23.
Article em En | MEDLINE | ID: mdl-37296576
ABSTRACT
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.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Cardiomiopatias Limite: Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Cardiomiopatias Limite: Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2023 Tipo de documento: Article