A New Variant in the MYH11 Gene in a Familial Case of Thoracic Aortic Aneurysm

Pucci, Lorenzo; Pointet, Alexandra; Good, Jean-Marc; Davoine, Emeline; Cina, Viviane; Zanchi, Fabio; Déglise, Sebastien; Duchosal, Lucia Mazzolai; Kirsch, Matthias

doi:10.1016/j.athoracsur.2019.07.030

Cited by 10 publications

(5 citation statements)

References 7 publications

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“…Cardiovascular / cerebrovascular manifestation The patient reported no gastrointestinal symptoms suggestive of VM, CIPO, or MMIHS, nor any recurrent fractures, visual disturbances, hypoacusis, stroke, urinary problems, or renal disease, as previously reported in MYH11 mutation carriers (Table 1) [9][10][11][12][13][14][15][16][17][18][19][20]. Whether Parkinson syndrome was due to cerebrovascular involvement or another cause remains controversial.…”

Section: Age (Y) Sex Variant Dosage Phenotype Referencementioning

confidence: 57%

“…The patient is of interest for a novel heterozygous variant of MYH11, which manifested phenotypically as aortic aneurysm, Parkinson syndrome, and noncompaction. Whether the detected heterozygous MYH11 variant was actually responsible for the clinical manifestations remains speculative, but several previous studies reported that heterozygous MYH11 variants can be pathogenic (Table 1) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Except for aortic aneurysm [7,8], the other clinical manifestations of the index patient were not reported in association with MYH11 variants.…”

Section: Discussionmentioning

confidence: 96%

“…Chromosomal rearrangements involving the MYH11 gene are associated with acute myeloid leukaemia and sarcoma [2]. Mutations in MYH11 are associated with multisystem disease, predominantly presenting as visceral myopathy (VM) [3], megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) [4,5], chronic intestinal pseudo-obstruction (CIPO) [6], and familial thoracic aortic aneurysm and dissection [7,8] but also with various other features [9][10][11][12][13][14][15][16][17][18][19][20]. Aortic aneurysm, noncompaction, also known as left ventricular hypertrabeculation (LVHT), and Parkinson syndrome have not been reported in association with MYH11 variants.…”

Section: Introductionmentioning

confidence: 99%

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Early Onset Parkinson Syndrome, Type A Aortic Aneurysm and Noncompaction Associated With the Novel Variant c.2225C>T in MYH11: A Case Report

Finsterer,

Mehri

2023

Cureus

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Aortic aneurysm, left ventricular noncompaction, and early onset Parkinson syndrome have not been reported in association with MYH11 variants. The patient is a 44-year-old male who developed a progressive ascending aortic aneurysm at age 30, requiring aortic repair at the age of 40. In addition, he developed Parkinson syndrome at the age of 37. He also suffered from myopia, hypothyroidism, arterial hypertension, hyperlipidemia, pre-diabetes, hyperbilirubinemia, obstructive sleep apnea syndrome (OSAS), and muscle cramps. Echocardiography and cardiac MRI showed left ventricular noncompaction. Genetic analysis revealed the novel heterozygous variant c.2225C>T (p.Ala742Val) in MYH11. Family history was positive for arterial hypertension (mother), carcinoma (brother), and diabetes (sister, father). There was consanguinity between the parents. With appropriate treatment, Parkinson syndrome and cardiac anomalies remained stable and there were no complications due to noncompaction or aortic repair. Considering that embryonic vascularisation may be involved in the pathophysiology of noncompaction and that MYH11 is expressed in the myocardium, a causal relationship between the MYH11 variant and noncompaction is conceivable.In conclusion, this is the first case showing an aortic aneurysm associated with noncompaction and Parkinson syndrome in a carrier of the novel, heterozygous variant c.2225C>T in MYH11. Carriers of MYH11 variants should be prospectively and systematically screened for multisystem diseases as soon as the genetic defect is discovered in order not to delay any necessary treatment. First-degree relatives should be screened for the MYH11 variant of a family member to track the trait of inheritance and confirm its pathogenicity.

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Section: Age (Y) Sex Variant Dosage Phenotype Referencementioning

confidence: 57%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Early Onset Parkinson Syndrome, Type A Aortic Aneurysm and Noncompaction Associated With the Novel Variant c.2225C>T in MYH11: A Case Report

Finsterer,

Mehri

2023

Cureus

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“…But no existing study has found that SPP1 is directly related to AD. MYH11 gene is involved in vascular contractility and vascular wall stability ( 43 , 44 ). For instance, it can decrease the proliferation and enhance the apoptosis of SMCs ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Key m6A Modification Related Genes and Immune Infiltrates in Human Aortic Dissection

Yin

Zhang

Guo

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveTo identify the feature of N6-methyladenosine (m6A) methylation modification genes in acute aortic dissection (AAD) and explore their relationships with immune infiltration.MethodsThe GSE52093 dataset including gene expression data from patients with AAD and healthy controls was downloaded from Gene Expression Omnibus (GEO) database in order to obtain the differentially expressed genes (DEGs). The differentially methylated m6A genes were obtained from the GSE147027 dataset. The differentially expressed m6A-related genes were obtained based on the intersection results. Meanwhile, the protein-protein interaction (PPI) network of differentially expressed m6A-related genes was constructed, and hub genes with close relationships in the network were selected. Later, hub genes were verified by using the GSE153434 dataset. Thereafter, the relationships between these genes and immune cells infiltration were analyzed.ResultsA total of 279 differentially expressed m6A-related genes were identified in the GSE52093 and GSE147027 datasets. Among them, 94 genes were up-regulated in aortic dissection (AD), while the remaining 185 were down-regulated. As indicated by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, these genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs). The seven hub genes, namely, DDX17, CTGF, FLNA, SPP1, MYH11, ITGA5 and CACNA1C, were all confirmed as the potential biomarkers for AD. According to immune infiltration analysis, it was found that hub genes were related to some immune cells. For instance, DDX17, FLNA and MYH11 were correlated with Macrophages M2.ConclusionOur study identifies hub genes of AD that may serve as the potential biomarkers, illustrates of the molecular mechanism of AD, and provides support for subsequent research and treatment development.

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“…Familiarity for thoracic aneurysm led us to require genetic testing. A MYH11 mutation was found, these mu-tations, which encode smooth muscle cell isoform of the myosin heavy chain 11, are responsible for thoracic aorta aneurysms/ dissections, either in association with patent ductus arteriosus or with coronary artery aneurysms, with an autosomal dominant inheritance (4,5). We cannot exclude in our patient a possible contribution of this mutation in determining coronary artery aneurysms.…”

mentioning

confidence: 99%