The correlation between spinal and chest wall deformities and pulmonary function in Marfan syndrome

Otremski, Hila; Widmann, Roger F.; Maio, Mary F Di; Ovadia, Dror

doi:10.1302/1863-2548.14.200076

Cited by 10 publications

(8 citation statements)

References 33 publications

(44 reference statements)

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“…Our study revealed 66 DMPs allocated to 42 genes enriched in cardiomyopathy, and three DMPs annotated to HLA-DRB1 and FBXO32 were associated with clinical events of cardiac surgery. On the other hand, pulmonary involvement is observed in approximately 63% of MFS patients, characterized by either restrictive or obstructive disease resulting from spinal deformities or abnormal lung parenchyma [31][32][33][34][35]. In our study, DMGs enriched in vital capacity, including 38 CpG sites, among which cg01160692 (NRG1) exhibited the strongest association with FEV1% predicted.…”

Section: Discussionmentioning

confidence: 60%

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

Zheng

Chen

et al. 2023

Preprint

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Background Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin-1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs). Methods The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co‑expression network analysis (WGCNA) was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS. Results Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) and cg00259849 (CSMD1) exhibited an inverse correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation and chondrocyte proliferation, respectively. Conclusions Taken together, our systems-level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

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Section: Discussionmentioning

confidence: 60%

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

Zheng

Chen

et al. 2023

Preprint

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“…However, the presence of kyphosis has been shown to increase the odds of IVDE in the thoracic vertebral column, and scoliosis has been associated with more caudal lumbar disc extrusions 17 . Interestingly, vertebral deformities in people have been associated with compromised pulmonary function; specifically, increasing thoracic spinal curvature was associated with diminished total lung capacity 18,19 . In our study population, dogs with vertebral malformations were not more likely to experience respiratory compromise.…”

Section: Discussionmentioning

confidence: 66%

“…17 Interestingly, vertebral deformities in people have been associated with compromised pulmonary function; specifically, increasing thoracic spinal curvature was associated with diminished total lung capacity. 18,19 In our study population, dogs with vertebral malformations were not more likely to experience respiratory compromise. However, future larger studies to evaluate the severity of kyphosis and compare this with airway conformation and pulmonary function would be worthwhile.…”

Section: Discussionmentioning

confidence: 76%

Respiratory compromise in French bulldogs presented with intervertebral disc extrusion

Foster,

West,

Butterfield

et al. 2023

Veterinary Record

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BackgroundFrench bulldogs hospitalised for the management of intervertebral disc extrusion (IVDE) are frequently affected by respiratory compromise, typically brachycephalic‐associated upper respiratory obstruction and/or aspiration events. We evaluated the occurrence of such respiratory compromise events in French bulldogs presented to two referral hospitals.MethodsClinical data for French bulldogs diagnosed with IVDE were retrospectively collated, including severity of neurological deficits, neuroanatomical localisation, diagnosis, details of respiratory compromise, treatment and outcome.ResultsA total of 306 dogs diagnosed with IVDE were included. Sixty dogs (19.6%) experienced respiratory compromise, of which 31 dogs (10.1%) progressed to cyanosis, collapse or respiratory arrest.LimitationsThe study was limited by its retrospective nature. Furthermore, the duration of hospitalisation was not evaluated and the decision for euthanasia was often multifactorial.ConclusionOne in five French bulldogs presented with IVDE experienced respiratory compromise. The detrimental welfare effects of this warrant further discussion.

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“…Pulmonary involvement is observed in approximately 63% of MFS, and it is characterized by either restrictive or obstructive lung disease resulting from spinal deformities or abnormal lung parenchyma. [39][40][41][42][43] In our study, we identified DMGs enriched in vital capacity, including 38 CpG sites. Among these, cg01160692 (HIC1), cg10109763 (NRG1), cg23774988 (ETS1), cg10975399 (ERC2), and cg13436558 (EBF1) showed the strongest association with FEV1% predicted.…”

Section: Discussionmentioning

confidence: 99%

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

Zheng,

Xu,

Chen

et al. 2024

JOR Spine

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BackgroundMarfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin‐1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs).MethodsThe Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation‐regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co‐expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS.ResultsOur study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation.ConclusionsTaken together, our systems‐level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

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The correlation between spinal and chest wall deformities and pulmonary function in Marfan syndrome

Cited by 10 publications

References 33 publications

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

Respiratory compromise in French bulldogs presented with intervertebral disc extrusion

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis

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