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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-2-1
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pubmed:abstractText |
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 WTNKX2-1, 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".
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1098-1004
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pubmed:author |
pubmed-author:BroutinIsabelleI,
pubmed-author:CarréAuroreA,
pubmed-author:CastanetMireilleM,
pubmed-author:ClementAnnickA,
pubmed-author:CounilFrançoisF,
pubmed-author:EpaudRalphR,
pubmed-author:FeldmannDelphineD,
pubmed-author:GuillotLoïcL,
pubmed-author:JaubertFrancisF,
pubmed-author:PolakMichelM,
pubmed-author:SzinnaiGaborG,
pubmed-author:TronElodieE
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pubmed:copyrightInfo |
(c) 2009 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E1146-62
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pubmed:dateRevised |
2010-6-16
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pubmed:meshHeading |
pubmed-meshheading:20020530-Abnormalities, Multiple,
pubmed-meshheading:20020530-Amino Acid Sequence,
pubmed-meshheading:20020530-Base Sequence,
pubmed-meshheading:20020530-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:20020530-Cell Line, Tumor,
pubmed-meshheading:20020530-Child,
pubmed-meshheading:20020530-Child, Preschool,
pubmed-meshheading:20020530-DNA,
pubmed-meshheading:20020530-Fatal Outcome,
pubmed-meshheading:20020530-Female,
pubmed-meshheading:20020530-Gene Expression Regulation,
pubmed-meshheading:20020530-Humans,
pubmed-meshheading:20020530-Infant,
pubmed-meshheading:20020530-Infant, Newborn,
pubmed-meshheading:20020530-Lung Diseases, Interstitial,
pubmed-meshheading:20020530-Molecular Sequence Data,
pubmed-meshheading:20020530-Mutant Proteins,
pubmed-meshheading:20020530-Mutation,
pubmed-meshheading:20020530-Nuclear Proteins,
pubmed-meshheading:20020530-Organ Specificity,
pubmed-meshheading:20020530-Pregnancy,
pubmed-meshheading:20020530-Promoter Regions, Genetic,
pubmed-meshheading:20020530-Protein Binding,
pubmed-meshheading:20020530-Pulmonary Surfactant-Associated Proteins,
pubmed-meshheading:20020530-Syndrome,
pubmed-meshheading:20020530-Thyroid Gland,
pubmed-meshheading:20020530-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in "Brain-Lung-Thyroid Syndrome".
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pubmed:affiliation |
INSERM UMR 938, UPMC, Université Paris 6, France.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
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