Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_29E186913C08
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.
Périodique
Human Mutation
Auteur(s)
Callewaert B., Su C.T., Van Damme T., Vlummens P., Malfait F., Vanakker O., Schulz B., Mac Neal M., Davis E.C., Lee J.G., Salhi A., Unger S., Heimdal K., De Almeida S., Kornak U., Gaspar H., Bresson J.L., Prescott K., Gosendi M.E., Mansour S., Piérard G.E., Madan-Khetarpal S., Sciurba F.C., Symoens S., Coucke P.J., Van Maldergem L., Urban Z., De Paepe A.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Statut éditorial
Publié
Date de publication
2013
Volume
34
Numéro
1
Pages
111-121
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish. PDF type: Research article
Résumé
Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms.
Pubmed
Web of science
Création de la notice
21/03/2013 17:48
Dernière modification de la notice
03/03/2018 15:22
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