LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix

Ramona Haji-Seyed-Javadi, Sahar Jelodari-Mamaghani, Seyed Hassan Paylakhi, Shahin Yazdani, Naveed Nilforushan, Jian Bing Fan, Brandy Klotzle, Mohammad Jafar Mahmoudi, Mohammad Jafar Ebrahimian, Noori Chelich, Ehsan Taghiabadi, Kambiz Kamyab, Catherine Boileau, Coro Paisan-Ruiz, Mostafa Ronaghi, Elahe Elahi

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109 Scopus citations

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 ttributed to MFS-related phenotypes, including ocular manifestations, mitral valve pro disruptions in the ECM. Heterozygous c.1642C >T (p.Arg548*) possibly conolapse, and pectus excavatum, but was not cause of MFS.

Original languageEnglish
Pages (from-to)1182-1187
Number of pages6
JournalHuman Mutation
Volume33
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Extracellular matrix
  • LTBP2
  • Marfan syndrome
  • Microfibrils
  • Weill-Marchesani syndrome

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