ArticleCirculation. Cardiovascular genetics2010
Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.
Article in Circulation. Cardiovascular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- Truncating Titin and Lamin A/C Variants in Anthracycline-Induced Cardiomyopathy.JACC. Advances · 2026Article
- Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of functionNucleus (Austin, Tex.) · 2025Review
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- PIGB maintains nuclear lamina organization in skeletal muscle of Drosophila.The Journal of cell biology · 2024Article
- A Clinical Diagnosis of Laminopathy without Systolic Dysfunction: When Does Nuclei Malformation Start?Internal medicine (Tokyo, Japan) · 2024Article
- How Functional Genomics Can Keep Pace With VUS Identification.Frontiers in cardiovascular medicine · 2022Review
- A deep hybrid learning pipeline for accurate diagnosis of ovarian cancer based on nuclear morphology.PloS one · 2022Article
- Most myopathic lamin variants aggregate: a functional genomics approach for assessing variants of uncertain significance.NPJ genomic medicine · 2021Article
- High-resolution 3D fluorescent imaging of intact tissues.International journal of cardiology and cardiovascular diseases · 2021Article
- Lamin A mutation impairs interaction with nucleoporin NUP155 and disrupts nucleocytoplasmic transport in atrial fibrillation.Human mutation · 2019Article
- Skeletal Muscle Dystrophy mutant of lamin A alters the structure and dynamics of the Ig fold domain.Scientific reports · 2018Article
- Multigenic Disease and Bilineal Inheritance in Dilated Cardiomyopathy Is Illustrated in Nonsegregating LMNA Pedigrees.Circulation. Genomic and precision medicine · 2018Article
- Elevated dual specificity protein phosphatase 4 in cardiomyopathy caused by lamin A/C gene mutation is primarily ERK1/2-dependent and its depletion improves cardiac function and survival.Human molecular genetics · 2018Article
- Deleterious assembly of the lamin A/C mutant p.S143P causes ER stress in familial dilated cardiomyopathy.Journal of cell science · 2016Article
- Assessment of incidental findings in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics.Genetics in medicine : official journal of the American College of Medical Genetics · 2015Article
- A novel human R25C-phospholamban mutation is associated with super-inhibition of calcium cycling and ventricular arrhythmia.Cardiovascular research · 2015Article
- Return of genetic results in the familial dilated cardiomyopathy research project.Journal of genetic counseling · 2013Article
- Temporal relationship of conduction system disease and ventricular dysfunction in LMNA cardiomyopathy.Journal of cardiac failure · 2013Article
- Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations.Molecular biology of the cell · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMutations in the LMNA gene, encoding lamins A/C, represent a significant cause of dilated cardiomyopathy. We recently identified 18 protein-altering LMNA variants in a cohort of 324 unrelated patients with dilated cardiomyopathy. However, at least one family member with dilated cardiomyopathy in each of 6 pedigrees lacked the LMNA mutation (nonsegregation), whereas small sizes of 5 additional families precluded definitive determinations of segregation, raising questions regarding contributions by those variants to disease. METHODS AND
resultsWe have consequently expressed, in COS7 cells, GFP-prelamin A (GFPLaA) fusion constructs incorporating the 6 variants in pedigrees with nonsegregation (R101P, A318T, R388H, R399C, S437Hfsx1, and R654X), the 4 variants in pedigrees with unknown segregation (R89L, R166P [in 2 families], I210S, R471H), and 3 additional missense variants (R190Q, E203K, and L215P) that segregated with disease. Confocal immunofluorescence microscopy was used to characterize GFP-lamin A localization and nuclear morphology. Abnormal phenotypes were observed for 10 of 13 (77%) variants (R89L, R101P, R166P, R190Q, E203K, I210S, L215P, R388H, S437Hfsx1, and R654X), including 4 of 6 showing nonsegregation and 3 of 4 with uncertain segregation. All 7 variants affecting coil 1B and the lamin A-only mutation, R654X, exhibited membrane-bound GFP-lamin A aggregates and nuclear shape abnormalities. Unexpectedly, R388H largely restricted GFP-lamin A to the cytoplasm. Equally unexpected were unique streaked aggregates with S437Hfsx1 and giant aggregates with both S437Hfsx1 and R654X.
conclusionsThis work expands the recognized spectrum of lamin A localization abnormalities in dilated cardiomyopathy. It also provides evidence supporting pathogenicity of 10 of 13 tested LMNA variants, including some with uncertain or nonsegregation.
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