Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene

Zaragoza, Michael V.; Nguyen, Christopher; Widyastuti, Halida P.; McCarthy, Linda A.; Grosberg, Anna

doi:10.3390/cells6040040

Cited by 8 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, majority of the LMNA-CM individuals are below the trend-line, which explains the aggregated average percent defective for LMNA-CM and LMNA-CM-A groups. From clinical data [ 4 , 9 , 10 ], we knew that the older patients in the cohort (LMNA-CM) developed heart disease later in life. Therefore, we plotted the difference between each patient’s cells’ dysmorphic nuclei percentage and the predicted value based on the control trend line (green arrow, Fig 4A ) against the age at which patients first presented with heart disease symptoms ( Fig 4B ).…”

Section: Resultsmentioning

confidence: 99%

“…Human fibroblast cells were collected from three families with different mutations of heterozygous LMNA splice-site mutation (c.357-2A>G) [ 4 ] (Family A); LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4 [ 10 ] (Family B); LMNA missense mutation (c.1003C>T, pR335W) in exon 6 [ 9 ] (Family C). Moreover, related individuals’ fibroblast cells in each family were collected as mutation-negative controls.…”

Section: Methodsmentioning

confidence: 99%

“…This is especially interesting as some nuclear envelope protein mutations lead to organ specific pathologies in patients. For example, there are a variety of LMNA mutations including heterozygous splice site, nonsense, and missense mutation, which cause diverse heart diseases with no other major pathologies [ 4 , 9 , 10 ]. Furthermore, even patients with the same mutation can exhibit a variety of heart disease symptoms with different presentation ages from 36–54 years [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations

et al. 2017

Self Cite

View full text Add to dashboard Cite

Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G), LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4, LMNA missense mutation (c.1003C>T, pR335W) in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method’s utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Family studies have revealed that there is a genetic component with manifestation of palmar and plantar fibromatosis. Zaragoza et al described the novel co-occurrence of palmar and plantar fibromatosis and LMNA-related cardiac disease in a family with a previously described nonsense mutation, LMNA c.736C>T (p. Gln246Stop) [32]. A novel, heterozygous missense variant (c.230T>C, p. Val77Ala) in the Asteroid Homolog 1 (ASTE1) gene has been revealed as a potential risk factor in fibrotic disease [32].…”

Section: Clinical Appearancesmentioning

confidence: 99%

“…Zaragoza et al described the novel co-occurrence of palmar and plantar fibromatosis and LMNA-related cardiac disease in a family with a previously described nonsense mutation, LMNA c.736C>T (p. Gln246Stop) [32]. A novel, heterozygous missense variant (c.230T>C, p. Val77Ala) in the Asteroid Homolog 1 (ASTE1) gene has been revealed as a potential risk factor in fibrotic disease [32]. They suggest that ASTE1 may contribute to the increased risk for palmar/plantar fibromatosis in patient with Lamin A/C haploinsufficiency [32].…”

Section: Clinical Appearancesmentioning

confidence: 99%

High-Resolution Ultrasonographic Appearances in Superficial Fibromatoses: Palmar and Plantar Diseases

Fujioka¹

2020

BJSTR

View full text Add to dashboard Cite

Dermatologic ultrasound imaging has been rapidly growing in recently years [1,2]. Currently, ultrasonography (US) studies for superficial fibromatoses, palmar fibromatosis, namely Dupuytren's disease [3] and plantar disease, namely Ledderhose disease [4] which are located in the subcutaneous tissue have been described in ultrasound field. Dupuytren's disease is a routine for the dermatologist, because patient with subcutaneous nodule may firstly visit a dermatologist. In this review, the author provides an update on the characteristic US appearances in superficial fibromatoses, palmar and plantar diseases. Dermatological UltrasoundThe international working group, namely DERMUS (Dermatologic Ultrasound) was formed and provided the guidelines [1] and proposed for an assessment training program [2]. Currently, US reports for palmar fibromatosis, namely Dupuytren's disease [3]and plantar disease, namely Ledderhorse disease [4] which are soft tissue tumors have been described in ultrasound field. We usually perform US studies for dermatologic fields with a high-resolution, broad-band (5MHz-18MHz) linear transducer (Nobulus Hitachi, Ltd.Tokyo, Japan). We have also provided several reports of the dermatologic lesion [5][6][7][8][9][10][11][12][13][14][15][16]. Normal Skin ElasticityThe author has previously described anatomy in dermatological ultrasound [16]. Klauser et al. [17] suggested that red is used to represent softer tissues, blue represents harder tissues, and yellow or green represent intermediate tissue elasticity on sonoelastography. The dermis consisting of connective tissue, nerves, blood, and lymphatic vessels, gland, mast cells, fibroblasts, histiocytes [18] represents blue color, showing hard nature, namely, low elasticity. While the subcutaneous fat tissue shows red color, consistent with soft nature, suggesting high elasticity, and reflecting contents of adipose cells [18] on RTE. Yang et al. [19] also studied a reference range of normal skin elasticity evaluated by share wave elastography (SWE) in healthy subjects to interpret results in patients with systemic scleroderma. They described that

show abstract

A Study of Gene Expression, Structure, and Contractility of iPSC-Derived Cardiac Myocytes from a Family with Heart Disease due to LMNA Mutation

et al. 2021

Self Cite

View full text Add to dashboard Cite

Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients with LMNA mutations have highly variable presentation of heart disease progression and type. In vitro patient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment. We hypothesized that integrating single cell RNA sequencing (scRNA-seq) with analysis of the tissue architecture and contractile function would elucidate some of the probable mechanisms. To test this, we investigated five iPSC-CM lines, three controls and two patients with a (c.357-2A>G) mutation. The patient iPSC-CM tissues had significantly weaker stress generation potential than control iPSC-CM tissues demonstrating the viability of our in vitro approach. Through scRNA-seq, differentially expressed genes between control and patient lines were identified. Some of these genes, linked to quantitative structural and functional changes, were cardiac specific, explaining the targeted nature of the disease progression seen in patients. The results of this work demonstrate the utility of combining in vitro tools in exploring heart disease mechanics.

show abstract

Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene

Cited by 8 publications

References 37 publications

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations

Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations

High-Resolution Ultrasonographic Appearances in Superficial Fibromatoses: Palmar and Plantar Diseases

A Study of Gene Expression, Structure, and Contractility of iPSC-Derived Cardiac Myocytes from a Family with Heart Disease due to LMNA Mutation

Contact Info

Product

Resources

About