Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress

Tarocco, Anna; Ballardini, Elisa; Contiero, Maria Raffaella; Garani, Giampaolo; Fanaro, Silvia

doi:10.1155/2015/591783

Cited by 6 publications

(6 citation statements)

References 10 publications

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“…We then reviewed a total of 48 full‐text articles out of which 14 were deemed ineligible for inclusion (i.e., articles were editorials or review articles, no mutations were reported, cases were included in other publications, or there were insufficient phenotypic detail). Three articles were excluded due to uncertainty as to whether the reported mutations were likely to be disease‐causing. One article was excluded because it had been retracted by the authors .…”

Section: Methodsmentioning

confidence: 99%

A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy

et al. 2016

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Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2017;52:57-68. © 2016 Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy

et al. 2016

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“…15 In contrast, the Case 7 SFTPC variant has been more well-characterized in the literature but similarly has weak evidence for pathogenicity in neonates as well as adults as there is no predicted effect on splicing (rs79440568, gnomAD frequency 0.0027). 14,[16][17][18] The ABCA3 single nucleotide missense mutation seen in Case 3 has also been shown in an in vitro model to have reduced ATPase activity without affecting surfactant trafficking or production. 19 Human data shows two entries in the NIH ClinVar Database, deemed to have "uncertain clinical significance" (rs117603931, gnomAD frequency 0.005667).…”

Section: Discussionmentioning

confidence: 93%

“…The SFTPB variant in Case 8 is a single nucleotide variant that has been reported in 4 patients in the NIH ClinVar Database and is described as benign or likely benign (rs35049407; gnomAD frequency 0.00207) 15 . In contrast, the Case 7 SFTPC variant has been more well‐characterized in the literature but similarly has weak evidence for pathogenicity in neonates as well as adults as there is no predicted effect on splicing (rs79440568, gnomAD frequency 0.0027) 14,16–18 . The ABCA3 single nucleotide missense mutation seen in Case 3 has also been shown in an in vitro model to have reduced ATPase activity without affecting surfactant trafficking or production 19 .…”

Section: Discussionmentioning

confidence: 99%

Lung biopsy in infants with severe bronchopulmonary dysplasia

Callaway

Wang

Lingappan

et al. 2023

Pediatric Pulmonology

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Introduction Lung biopsy is infrequently performed in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities or identify those with an extremely poor prognosis. Both might alter the clinical management of some infants diagnosed with BPD. Methods In this tertiary referral center, we drew on a retrospective cohort of 308 preterm infants with severe BPD. Of these, nine underwent lung biopsy between 2012 and 2017. We aimed to assess the indication for lung biopsy, the prior clinical history, safety of the procedure, and describe the biopsy findings. Finally, we considered management decisions in relation to the biopsy results in these patients. Results All nine infants undergoing biopsy survived the procedure. The mean gestational age and birth weight of the nine patients were 30 ± 3 (range 27−34) weeks and 1421 ± 571 (range 611−2140) grams. All infants received serial echocardiograms to assess pulmonary hypertension, genetic testing, and computed tomography angiography (CTA) before biopsy. In all nine patients moderate to severe alveolar simplification was present and eight had some degree of pulmonary interstitial glycogenosis (PIG) ranging from focal to diffuse. Following biopsy, two infants with PIG received high dose systemic steroids and two separate infants had care redirected. Conclusion In our cohort, lung biopsy was safe and well tolerated. Findings from lung biopsy may aid decision making in selected patients as a part of a step‐wise diagnostic algorithm.

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“…Heterozygous SP-B knockout mice showed decreased pulmonary compliance and the increased susceptibility to lung injury and inflammation (28). SP-C knockout mice appeared normal at birth but demonstrated altered surfactant stability and abnormalities in lung mechanics at adulthood (27). Recently, SP-D has been shown to be involved in the regulation of innate and adaptive immunity, contributing to allergic inflammation and pulmonary fibrosis (24).…”

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confidence: 99%

Epithelial disruption of Gab1 perturbs surfactant homeostasis and predisposes mice to lung injuries

Wang

Qin

Liang

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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GRB2-associated-binding protein 1 (Gab1) belongs to Gab adaptor family, which integrates multiple signals in response to the epithelial growth factors. Recent genetic studies identified genetic variants of human Gab1 gene as potential risk factors of asthmatic inflammation. However, the functions of Gab1 in lungs remain largely unknown. Alveolar type-II cells (AT-IIs) are responsible for surfactant homeostasis and essentially regulate lung inflammation following various injuries (3). In this study, in vitro knockdown of Gab1 was shown to decrease the surfactant proteins (SPs) levels in AT-IIs. We further examined in vivo Gab1 functions through alveolar epithelium-specific Gab1 knockout mice (Gab1). In vivo Gab1 deficiency leads to a decrease in SP synthesis and the appearance of disorganized lamellar bodies. Histological analysis of the lung sections in Gab1 mice shows no apparent pathological alterations or inflammation. However, Gab1 mice demonstrate inflammatory responses during the LPS-induced acute lung injury. Similarly, in mice challenged with bleomycin, fibrotic lesions were found to be aggravated in Gab1 These observations suggest that the abolishment of Gab1 in AT-IIs impairs SP homeostasis, predisposing mice to lung injuries. In addition, we observed that the production of surfactants in AT-IIs overexpressing Gab1 mutants, in which Shp2 phosphatase and PI3K kinase binding sites have been mutated (Gab1, Gab1), has been considerably attenuated. Together, these findings provide the direct evidence about the roles of docking protein Gab1 in lungs, adding to our understanding of acute and interstitial lung diseases caused by the disruption of alveolar SP homeostasis.

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Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress

Cited by 6 publications

References 10 publications

A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy

A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy

Lung biopsy in infants with severe bronchopulmonary dysplasia

Epithelial disruption of Gab1 perturbs surfactant homeostasis and predisposes mice to lung injuries

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