title: LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix.
abstract: Latent transforming growth factor (TGF) beta-binding protein 2 (LTBP2) is an extracellular matrix (ECM) protein that associates with fibrillin-1 containing microfibrils. Various factors prompted considering LTBP2 in the etiology of isolated ectopia lentis and associated conditions such as Weill-Marchesani syndrome (WMS) and Marfan syndrome (MFS). LTBP2 was screened in 30 unrelated Iranian patients. Mutations were found only in one WMS proband and one MFS proband. Homozygous c.3529G>A (p.Val1177Met) was shown to cause autosomal recessive WMS or WM-like syndrome by several approaches, including homozygosity mapping. Light, fluorescent, and electron microscopy evidenced disruptions of the microfibrillar network in the ECM of the proband's skin. In conjunction with recent findings regarding other ECM proteins, the results presented strongly support the contention that anomalies in WMS patients are due to disruptions in the ECM. Heterozygous c.1642C >T (p.Arg548*) possibly contributed to MFS-related phenotypes, including ocular manifestations, mitral valve prolapse, and pectus excavatum, but was not cause of MFS.
authors.affiliation: School of Biology, University College of Science, University of Tehran, Tehran, Iran.
authors.forename: Ramona
authors.initials: R
authors.lastname: Haji-Seyed-Javadi
authors.forename: Sahar
authors.initials: S
authors.lastname: Jelodari-Mamaghani
authors.forename: Seyed Hassan
authors.initials: SH
authors.lastname: Paylakhi
authors.forename: Shahin
authors.initials: S
authors.lastname: Yazdani
authors.forename: Naveed
authors.initials: N
authors.lastname: Nilforushan
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.forename: Mohammad Jafar
authors.initials: MJ
authors.lastname: Mahmoudi
authors.forename: Mohammad Jafar
authors.initials: MJ
authors.lastname: Ebrahimian
authors.forename: Noori
authors.initials: N
authors.lastname: Chelich
authors.forename: Ehsan
authors.initials: E
authors.lastname: Taghiabadi
authors.forename: Kambiz
authors.initials: K
authors.lastname: Kamyab
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Coro
authors.initials: C
authors.lastname: Paisan-Ruiz
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D020894:Microfibrils / Q000378:metabolism; D009154:Mutation; D056846:Weill-Marchesani Syndrome / Q000209:etiology* / Q000235:genetics*
chemical_list: C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins