Two patients with the heterozygous R189H mutation in <i>ACTA2</i> and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome

Logeswaran, Thushiha; Friedburg, Christoph; Hofmann, Karoline; Akintuerk, Hakan; Biskup, Saskia; Graef, Michael; Rad, Ali Bahrami; Weber, Axel; Neubauer, Bernd A.; Schranz, Dietmar; Bouvagnet, Patrice; Lorenz, Birgit; Hahn, Andreas

doi:10.1002/ajmg.a.38329

Cited by 7 publications

(7 citation statements)

References 19 publications

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“…Another clinical study revealed that serum IFNG levels were significantly positively correlated with TG concentration in CHD patients, which could be involved in the development of atherosclerosis of the coronary artery [ 89 ]. ACTA2, the human aortic smooth muscle actin (SMA) gene typically expressed in VSMCs, contributes to vascular motility and contraction and may cause a variety of vascular diseases in the event of mutation, such as coronary artery disease and multisystemic smooth muscle dysfunction syndrome [ 90 , 91 ]. In experimental homozygous α-SMA knockout mice, decreased vascular contractility and reduced basal blood pressure were notable, suggesting the important role of α-SMA in maintaining vascular tone [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling

et al. 2020

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Traditional Chinese medicine (TCM) has evolved over several thousands of years, which has been shown to be efficacious in the treatment of ischemic heart disease. Three classical TCM prescriptions, namely Xuefu Zhuyu Decoction, Zhishi Xiebai Guizhi Decoction, and Gualou Xiebai Banxia Decoction, have been extensively used in the treatment of coronary heart disease (CHD). Based on molecular network modeling, we performed a comparative pharmacogenomic analysis to systematically determine the drug-targeting spectrum of the three prescriptions at molecular level. Wide-area target molecules of CHD were covered, which was a common feature of the three decoctions, demonstrating their therapeutic functions. Meanwhile, collective signaling involved metabolic/pro-metabolic pathways, driving and transferring pathways, neuropsychiatric pathways, and exocrine or endocrine pathways. These organized pharmacological disturbance was mainly focused on almost all stages of CHD intervention, such as anti-atherosclerosis, lipid metabolism, inflammation, vascular wall function, foam cells formation, platelets aggregation, thrombosis, arrhythmia, and ischemia-reperfusion injury. In addition, heterogeneity analysis of the global pharmacological molecular spectrum revealed that signaling crosstalk, cascade convergence, and key targets were tendentious among the three decoctions. After all, it is unadvisable to rank the findings on targeting advantages of the three decoctions. Comparative pharmacological evidence may provide an appropriate decoction scheme for individualized intervention of CHD.

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Section: Discussionmentioning

confidence: 99%

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling

et al. 2020

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“…ACTA2 mutation has been recently identified as a major cause of familial thoracic aortic aneurysm and ductus arteriosus aneurysm. 7 Several MYH11 mutations have been implicated in adults with thoracic aortic aneurysms and patent ductus arteriosus. 8 A dominant causal variant in MYH11 associated with smooth muscle dysfunction has been reported recently in families with chronic intestinal pseudoobstruction.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of congenital ductal aneurysm remains ill defined, although several theories have been postulated. 7 These include (a) delayed closure of the aortic end of the ductus, resulting in exposure of the ductal wall to systemic arterial pressure, (b) necrosis and mucoid degeneration of the media of the ductus, resulting in weakness of the wall, (c) congenital weakening of the ductal wall from defective elastin, resulting in abnormal intimal cushion formation, and (d) intrauterine constriction of the ductus close to the pulmonary end with post-stenotic dilation. In our patient, the likely mechanism of aneurysmal ductus is the failure to constrict after birth from defective smooth muscle myosin.…”

Section: Discussionmentioning

confidence: 99%

“…4 Spontaneous resolution of the ductal aneurysm is possible by one of two mechanisms: most due to progressive constriction and the remaining from thrombus formation. 7 However, severe and life-threatening complications have been reported. These include thromboembolic extension into the main pulmonary artery or the aorta, spontaneous rupture, erosion or compression of adjacent structures, and infection.…”

Section: Discussionmentioning

confidence: 99%

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Congenital ductus arteriosus aneurysm in association with MYH11 mutation: a case report

Ardhanari

Swaminathan

2020

Cardiol Young

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Congenital ductus arteriosus aneurysms develop in the third trimester of fetal life, possibly due to abnormal intimal cushion formation or elastin expression in the ductal wall. It is often diagnosed in infants before 2 months of age. Most have a benign course and resolve spontaneously. However, life-threatening complications have been reported. We report a case of large ductal aneurysm diagnosed incidentally in a neonate, in whom there was a novel mutation in the smooth muscle myosin protein gene—MYH11.

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“…Tables 1-4 summarizes the systemic features of the reported patients with MSMDS worldwide[8-16]. SMCs are widely distributed in the gastrointestinal tract, urinary tract, respiratory tract, uterus, iris, and other body parts.…”

Section: Discussionmentioning

confidence: 99%

Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature

Chen¹,

Wang²,

Hao³

et al. 2019

WJCC

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BACKGROUNDMultisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare genetic disease worldwide. The main mutation is the actin alpha 2 (ACTA2) gene p.R179H. In this paper, we report a Chinese MSMDS patient and systematically review the previous literature.CASE SUMMARYHere, we report a 9.6-month-old Chinese girl who was diagnosed with MSMDS based on her history and symptoms, such as recurrent cough, wheezing, and complications with congenital fixed dilated pupils. Chest high-resolution computed tomography revealed inhomogeneous lung transparency, obvious exudative lesions, and some lung fissures that were markedly thickened. Cranial magnetic resonance imaging excluded bleeding and infarction but showed abnormal signals in the centrum ovale majus and bilateral periventricular regions. Echocardiography only showed patent foramen ovale, and no patent ductus arteriosus, pulmonary artery dilatation, or pulmonary hypertension was found. Bronchoscopy indicated moderate bronchial malacia. These examinations in conjunction with the typical eye abnormality suggested a diagnosis of MSMDS, and sequencing of exon 6 of the ACTA2 gene demonstrated the heterozygous mutation c.536G>A, p.R179H. However, her parents’ gene analyses were normal.CONCLUSIONMSMDS is a rare genetic disease mainly caused by the mutation of the ACTA2 gene p.R179H. Early genetic diagnosis should be performed for children presenting with congenital fixed dilated pupils and patent ductus arteriosus. During the process of diagnosis and treatment, clinicians should be on high alert for cerebrovascular, cardiovascular, and pulmonary complications.

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Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome

Cited by 7 publications

References 19 publications

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling

Congenital ductus arteriosus aneurysm in association with MYH11 mutation: a case report

Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature

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