Filamin A (<i>FLNA</i>) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

Shelmerdine, Susan C.; Semple, Thomas; Wallis, Colin; Aurora, Paul; Moledina, Shahin; Ashworth, Michael; Owens, Cátherine M.

doi:10.1002/ppul.23695

Cited by 47 publications

(38 citation statements)

References 17 publications

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“…The mutation of FLNA has been shown to be associated with the neuronal migration, vascular function, connective tissue integrity, and skeletal development (Shelmerdine et al 2017); FLNA showed low expression in CRC patients and was significantly correlated with the incidence and development of CRC (Tian et al 2015). LBR, a transmembrane protein of the inner nuclear membrane, interacts with heterochromatin and B-type lamins through its nucleoplasmic aminoterminal domain and is phosphorylated throughout the cell cycle (Duband-Goulet et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients (v0.2)"

2018

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Objective The mechanism underlying colon cancer metastasis remain unclear. This study aimed to elucidate the genes alteration during the metastasis of colon cancer and identify genes that crucial to the metastasis and survival of colon cancer patients. Methods The dataset of primary and metastasis tissue of colon cancer, and dataset of high and low metastasis capability of colon cancer cells were selected as training cohort, and the overlapped differentially expressed genes (DEGs) were screened from the training cohort. The functional enrichment analysis for the overlapped DEGs was performed. The prognostic value of overlapped DEGs were analyzed in TCGA dataset, and a gene signature was developed using genes that related to the overall survival (OS). The prognostic value of the gene signature was further confirmed in a validation cohort. Results 184 overlapped DEGs were screened from the training cohort. Functional enrichment analysis revealed the significant gene functions and pathways of the overlapped DEGs. Four hub genes (OXCT1, ACTN4, IL-8, ITGA3) were identified using protein-protein network analysis. Six genes (ALDH2, NEDD9, FLNA, LBR, TWF1, SRSF1) were closely related to the OS of colon cancer patients. A gene signature was developed used these six genes based on their risk score, and the validation cohort indicated that the prognostic value of this gene signature was high in the prediction of colon cancer patients. Conclusions Our study demonstrates a gene profiles related to the metastasis of colon cancer, and identify a sixgene signature that acts as an independent biomarker on the prognosis of colon cancer.

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Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients (v0.2)"

2018

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“…The Filamin A protein is an actin-binding and scaffolding protein that binds to integrins and also interacts with CFTR [27]. Of interest, mutations in the FLNA gene result in interstitial lung disease, a severe respiratory illness [28]. The FLNA protein is required for optimal T cell homing into lymph nodes and inflamed tissues [29].…”

Section: Plos Onementioning

confidence: 99%

Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis

et al. 2020

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Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze-omic datasets in rare genetic diseases as patient cohorts are inevitably small.

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“…There is emerging recognition of a respiratory phenotype of this genetic disorder that occurs in infancy and has unique features, including cardiovascular manifestations (aortic-valve disease and dilatation, patent ductus arteriosus, and pulmonary hypertension) and pulmonary manifestations (emphysema and lung cysts alternating with atelectasis and tracheobronchomalacia or stenosis). [14][15][16][17][18][19][20][21] A recent review summarizes the cases reported in the literature to date. 22 Thus far, at least 18 cases of FLNA-related disease with this respiratory phenotype have been identified in infancy.…”

Section: Connective-tissue Disordersmentioning

confidence: 99%

“…The respiratory phenotype of FLNArelated disease is now considered to be a childhood interstitial lung disease. 21 The filamin A protein is thought to be important in the maturation of alveoli in embryologic life, a process that affects lung growth and development. Findings similar to bronchopulmonary dysplasia due to alveolar simplification have been noted.…”

Section: Connective-tissue Disordersmentioning

confidence: 99%

“…20 Since then, 17 additional case reports of lung disease have been described in the literature, but more cases are being recognized in the clinic, particularly in lung transplantation centers. [15][16][17][18][19][20][21][22]27 Of the 18 patients, 15 were female, which suggests that males are more likely to be severely affected and are less likely to survive to birth. All but 1 of these patients were born at full term.…”

Section: Agnos Tic Tes Tingmentioning

confidence: 99%

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Case 28-2019: A 22-Year-Old Woman with Dyspnea and Chest Pain

et al. 2019

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A 22-year-old woman was seen in the pediatric pulmonary clinic of this hospital because of chest pain, cough, and dyspnea on exertion. The patient had been well until she was 2 months of age, when an episode of bronchiolitis occurred. After this episode, repeated respiratory illnesses characterized by wheezing and cyanosis developed, and she was hospitalized frequently. The patient was subsequently evaluated by a pediatric pulmonologist at this hospital. Examination revealed decreased breath sounds at the apex of the right lung, and chest radiography revealed findings suggestive of congenital lobar emphysema of the right upper lobe. A blood test for alpha 1-antitrypsin deficiency was negative. Transthoracic echocardiography revealed right ventricular dilatation and hypertrophy, mild pulmonary arterial hypertension, and a small patent ductus arteriosus. When the patient was 24 months of age, a right upper lobectomy, coil embolization for the patent ductus arteriosus, and a biopsy of the right middle lobe were performed. Dr. Mari Mino-Kenudson: Histopathological examination of lung specimens revealed lobar emphysema of the right upper and middle lobes that was characterized by the presence of fewer alveoli than the number typically seen in normal lung tissue and hyperinflation of the existing alveoli (Fig. 1A). The number of bronchioles in the peripheral emphysematous areas was disproportionately low relative to the number of pulmonary vessels, and the central bronchi had mucus plugs that may have obliterated the bronchial lumens (Fig. 1B). In the hilum, the central bronchi had mucus plugs that resulted in partial obstruction of the bronchial lumens, but the amount and contour of the bronchial cartilage were normal (Fig. 1C). No diagnostic findings were consistent with pulmonary hypertension. There are two possible causes of lobar emphysema in this case: obstruction (either

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Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

Abstract: The progressive nature of the pulmonary aspect of this disorder and need for early aggressive supportive treatment make identification crucial to patient management and prognostic counseling.

Cited by 47 publications

References 17 publications

Peer Review #2 of "Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients (v0.2)"

Peer Review #2 of "Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients (v0.2)"

Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis

Case 28-2019: A 22-Year-Old Woman with Dyspnea and Chest Pain

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