New surfactant protein C gene mutations associated with diffuse lung disease

Guillot, Loïc; Epaud, Ralph; Thouvenin, Guillaume; Jonard, Laurence; Mohsni, A; Couderc, Rémy; Counil, F.; Blic, J. de; Taam, Rola Abou; Bourgeois, M. Le; Reix, Philippe; Flamein, Florence; Clément, Annick; Feldmann, Delphine

doi:10.1136/jmg.2009.066829

Cited by 98 publications

(75 citation statements)

References 20 publications

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“…Although linker domain mutations have been reported to have a less severe clinical expression than BRICHOS mutation in some series, 7,17 our own data and the literature do not necessarily support this concept. We found three BRICHOS domain rare variants in our series.…”

Section: Polarized Light Microscopycontrasting

confidence: 64%

“…Prevalence in pDLD series, as in ours, varies from 8 to 17%. 1, 3,6,7,19,26 SP-C mutations have been described in term 15,27 or late preterm infants with severe RDS, although this presentation is more typical of SP-B and ABCA3 biallelic mutations. 2 The typical presentation of SP-C defects consists of dyspnea, cough or wheezing with an onset between 2 and 12 months of age, gradual cyanosis and failure to thrive.…”

Section: Polarized Light Microscopymentioning

confidence: 99%

“…Clinical onset varies from birth to advanced adulthood, with variable severity and outcome. 7 Complex molecular mechanisms account in part for the phenotypic diversity of the disease. Environmental factors also have a key role in modulating the disease course, as carriers of the same mutation in a single pedigree may show a broad variability of onset and presentation.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations

et al. 2015

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Genetic defects of surfactant metabolism are associated with a broad range of clinical manifestations, from neonatal respiratory distress syndrome to adult interstitial lung disease. Early therapies may improve symptoms but diagnosis is often delayed owing to phenotype and genotype variability. Our objective was to characterize the cellular/ultrastructural correlates of surfactant protein C (SP-C) mutations in children with idiopathic diffuse lung diseases. We sequenced SFTPC -the gene encoding SP-C -SFTPB and ABCA3, and analyzed morphology, ultrastructure and SP expression in lung tissue when available. We identified eight subjects who were heterozygous for SP-C mutations. Median age at onset and clinical course were variable. None of the mutations were located in the mature peptide-encoding region, but were either in the pro-protein BRICHOS or linker C-terminal domains. Although lung morphology was similar to other genetic surfactant metabolism disorders, electron microscopy studies showed specific anomalies, suggesting surfactant homeostasis disruption, plus trafficking defects in the four subjects with linker domain mutation and protein misfolding in the single BRICHOS mutation carrier in whom material was available. Immunolabeling studies showed increased proSP-C staining in all cases. In two cases, amyloid deposits could be identified. Immunochemistry and ultrastructural studies may be useful for diagnostic purposes and for genotype interpretation.

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Section: Polarized Light Microscopycontrasting

confidence: 64%

Section: Polarized Light Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations

et al. 2015

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“…Recently, increasing numbers of reports have been published concerning surfactant protein C gene mutations and coexisting interstitial pneumonia, especially familial interstitial pneumonia (12)(13)(14)(15)(16)(17). Some of these reports showed the coexistence of PAP-like surfactant protein deposition and interstitial pneumonia.…”

Section: F I G U R E 3 a ) T H E F I N E G R A N U L A R Ma T E R Imentioning

confidence: 99%

A Young Woman with Interstitial Pneumonia and Coexisting Deposition of Surfactant Proteins

et al. 2010

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We report a 23-year-old woman with interstitial inflammation and fibrosis associated with deposition of surfactant proteins in the airways. Biopsy of the lung showed multiple focal lesions containing dilated airways with inflammation and fibrosis. Pale eosinophilic amorphous material, dense eosinophilic bodies and numerous cholesterin clefts were observed in the airways. Surfactant protein A (SP-A) was expressed in the amorphous material. SP-D was identified in the dense eosinophilic bodies and around the acicular clefts. The finding that surfactant depositions were anatomically coincident with the interstitial pneumonia suggests that surfactant depositions were closely related to the interstitial pneumonia.

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“…Genomic DNA was extracted from peripheral blood samples of the patient, her parents, and 61 healthy control subjects using the QIAamp DNA blood mini kit (Qiagen GmbH, Hilden, Germany). The coding exons of SFTPC were amplified by PCR using previously described primers (29). PCR products were confirmed by sequencing.…”

Section: Genetic Analysesmentioning

confidence: 99%

A novel surfactant protein C L55F mutation associated with interstitial lung disease alters subcellular localization of proSP-C in A549 cells

et al. 2015

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New surfactant protein C gene mutations associated with diffuse lung disease

Abstract: Our results confirm that SFTPC mutations are a frequent cause of diffuse lung disease, and that I73T is the most frequent SFTPC mutation associated with diffuse lung disease.

Cited by 98 publications

References 20 publications

Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations

Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations

A Young Woman with Interstitial Pneumonia and Coexisting Deposition of Surfactant Proteins

A novel surfactant protein C L55F mutation associated with interstitial lung disease alters subcellular localization of proSP-C in A549 cells

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