Interstitial lung disease in children – genetic background and associated phenotypes

Hartl, Dominik; Griese, Matthias

doi:10.1186/1465-9921-6-32

Cited by 60 publications

(46 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SFTPC mutations have been described before with severity varying from neonatal respiratory insufficiency [9] to children and adults with mild-to-severe ILD [3,[23][24][25]. In an elegant study, follow-up of five patients with SFTPC mutations was reported after three decades, as previously published cases can be genetically analysed later [10].…”

Section: Discussionmentioning

confidence: 50%

Genotype alone does not predict the clinical course ofSFTPCdeficiency in paediatric patients

et al. 2015

Self Cite

View full text Add to dashboard Cite

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised.We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations.17 patients (seven male) were followed over a median of 3 years (range 0.3-19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations ( p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94-197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were "sick-better" (2.8 years, range 0.8-19), seven patients were "sick-same" (6.5 years, 1.3-15.8) and three patients were "sick-worse" (0.3 years, 0.3-16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype.Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers. @ERSpublications Genotype alone does not predict the clinical course of surfactant protein C deficiency in children and young adults http://ow.ly/GRhCc

show abstract

Section: Discussionmentioning

confidence: 50%

Genotype alone does not predict the clinical course ofSFTPCdeficiency in paediatric patients

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…NKX2-1-p.L263fs induced neither SFTPC nor SFTPB promoter activation and had a dominant negative effect on wild-type NKX2-1, in accordance with the SP-B and SP-C protein levels in the BALF of our patient. Reduced amounts of SP-B and SP-C may be responsible for lung disease, as shown in patients with partial SP-B deficiency or SFTPC mutation-associated lung diseases [Nogee, 2004;Hartl and Griese, 2005]. The presence of SP-C and SP-B precursors, as well as the large amounts of β-actin revealed by Western blot analysis, may be explained in this case by alveolar damage resulting from altered surfactant metabolism.…”

Section: Discussionmentioning

confidence: 99%

NKX2-1mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in “Brain-Lung-Thyroid Syndrome”

et al. 2010

View full text Add to dashboard Cite

NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB and SFTPC, respectively). We identified and functionally characterized two new de novo NKX2-1 mutations c.493C>T (p.R165W) and c.786_787del2 (p.L263fs) in infants with closely similar severe interstitial lung disease (ILD), hypotonia, and congenital hypothyroidism. Functional analyses using A549 and HeLa cells revealed that NKX2-1-p.L263fs induced neither SFTPB nor SFTPC promoter activation and had a dominant negative effect on wild-type (WT) NKX2-1. In contrast, NKX2-1-p.R165W activated SFTPC, to a significantly greater extent than did WT NKX2-1, while SFTPB activation was only significantly reduced in HeLa cells. In accordance with our in vitro data, we found decreased amounts of SP-B and SP-C by western blot in bronchoalveolar lavage fluid (patient with p.L263fs) and features of altered surfactant protein metabolism on lung histology (patient with NKX2-1-p.R165W). In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in "Brain-Lung-Thyroid syndrome".

show abstract

“…Гид рофобный белок сурфактанта С, играющий важную роль в формировании, организации и функциониро вании сурфактнатной "пленки", необходим для ста билизации альвеол и равномерного распределения сурфактанта. Мутации в гене, кодирующем SFTP C, ассоциированы с различными вариациями семейной интерстициальной легочной пневмонии, включая идиопатический легочный фиброз [8] и неспецифи ческую интерстициальную пневмонию у взрослых и детей [9,10]. На сегодняшний день описаны и изу чаются значимые, сцеплено наследуемые полимор физмы N138T (А>C) и N186S (А>G) в гене SFTP C. Известно, что снижение или отсутствие активности гена SFTP C связано с прогрессирующей болезнью легких (в частности, у новорожденных) самых раз ных типов.…”

Section: заметки из практикиunclassified

A Case of Multiple Genetic Lesions in Different Systems of the Lung Defense

Дидковский¹,

Жарова²,

Каблашова³

et al. 2011

Pulʹmonologiâ (Mosk.)

View full text Add to dashboard Cite

Interstitial lung disease in children – genetic background and associated phenotypes

Cited by 60 publications

References 149 publications

Genotype alone does not predict the clinical course ofSFTPCdeficiency in paediatric patients

Genotype alone does not predict the clinical course ofSFTPCdeficiency in paediatric patients

NKX2-1mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in “Brain-Lung-Thyroid Syndrome”

A Case of Multiple Genetic Lesions in Different Systems of the Lung Defense

Contact Info

Product

Resources

About