Surfactant proteins in pediatric interstitial lung disease

Griese, Matthias; Lorenz, E; Hengst, Meike; Schams, Andrea; Wesselak, Traudl; Rauch, Daniela; Wittmann, Thomas; Kirchberger, Valerie; Escribano, Amparo; Schaible, T; Baden, Winfried; Schulze, Johannes; Krude, Heiko; Aslanidis, Charalampos; Schwerk, Nicolaus; Kappler, Matthias; Hartl, Dominik; Zarbock, Ralf

doi:10.1038/pr.2015.173

Cited by 26 publications

(20 citation statements)

References 39 publications

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“…G). This is concordance with previous studies, which showed reduction of SP‐C protein in BALs from patients with ABCA3 deficiency . The K1388N mutation was predicted to be malign and not tolerated by the algorithms Polyphen and SIFT.…”

Section: Resultsmentioning

confidence: 84%

Tools to explore ABCA3 mutations causing interstitial lung disease

Wittmann¹,

Schindlbeck²,

Höppner³

et al. 2016

Pediatr Pulmonol.

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Here we present a set of tools useful for categorizing different ABCA3 mutations according to their impact upon ABCA3 activity. Knowledge of the molecular defects and close correlation of in vitro and ex vivo data will allow us to define groups of mutations that can be targeted by small molecule correctors for restoring impaired ABCA3 transporter in the future. Pediatr Pulmonol. 2016;51:1284-1294. © 2016 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 84%

Tools to explore ABCA3 mutations causing interstitial lung disease

Wittmann¹,

Schindlbeck²,

Höppner³

et al. 2016

Pediatr Pulmonol.

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“…Patients were investigated for variants in exons 4 to 33 of the ABCA3 gene (NM_001089), in exons 1 to 11 of the SFTPB gene (NM_000542) and in exons 1 to 5 of the SFTPC gene (NM_003018) (22). Genomic DNA were amplified by PCR using the primers listed (Supplementary Table 4).…”

Section: Genetic Analysis For Abca3 Sftpc and Sftpbmentioning

confidence: 99%

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3

Wittmann¹,

Frixel²,

Höppner³

et al. 2016

Mol Med

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“…Interstitial lung diseases (ILD) in children comprise a broad array of chronic respiratory disorders with considerable morbidity and mortality (Griese et al., ). Several monogenetic causes, mainly associated with disturbances of the pulmonary surfactant system, have been identified (Hartl & Griese, ), including mutations in the genes coding for surfactant proteins ( SFTPC, SFTPB ) (Griese et al., ; Nogee, ), thyroid transcription factor‐1 ( NKX2‐1 ) (Kleinlein et al., ; Thorwarth et al., ), and ATP‐binding cassette subfamily A member 3 ( ABCA3 , MIM# 601615), while mutations in ABCA3 appear to be most frequent (Brasch et al., ; Saugstad et al., ).…”

Section: Introductionmentioning

confidence: 99%

ABCA3 missense mutations causing surfactant dysfunction disorders have distinct cellular phenotypes

Schindlbeck¹,

Wittmann²,

Höppner³

et al. 2018

Human Mutation

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Mutations in the ATP-binding cassette subfamily A member 3 (ABCA3) gene are the most common monogenetic cause of surfactant dysfunction disorders in newborns and interstitial lung diseases in children and young adults. Although the effect of mutations resulting in truncated or incomplete proteins can be predicted, the consequences of missense variants cannot be as easily. Our aim was to investigate the intracellular handling and disturbance of the cellular surfactant system in a stable cell model with several different clinically relevant ABCA3 missense mutations. We found that the investigated missense mutations within the ABCA3 gene affect surfactant homeostasis in different ways: first by disrupting intracellular ABCA3 protein localization (c.643C > A, p.Q215K; c.2279T > G, p.M760R), second by impairing the lipid transport of ABCA3 protein (c.875A > T, p.E292V; c.4164G > C, p.K1388N), and third by yet undetermined mechanisms predisposing for the development of interstitial lung diseases despite correct localization and normal lipid transport of the variant ABCA3 protein (c.622C > T, p.R208W; c.863G > A, p.R288K; c.2891G > A, p.G964D). In conclusion, we classified cellular consequences of missense ABCA3 sequence variations leading to pulmonary disease of variable severity. The corresponding molecular pathomechanisms of such ABCA3 variants may specifically be addressed by targeted treatments.

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Surfactant proteins in pediatric interstitial lung disease

Cited by 26 publications

References 39 publications

Tools to explore ABCA3 mutations causing interstitial lung disease

Tools to explore ABCA3 mutations causing interstitial lung disease

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3

ABCA3 missense mutations causing surfactant dysfunction disorders have distinct cellular phenotypes

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