TY - JOUR
T1 - LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix
AU - Haji-Seyed-Javadi, Ramona
AU - Jelodari-Mamaghani, Sahar
AU - Paylakhi, Seyed Hassan
AU - Yazdani, Shahin
AU - Nilforushan, Naveed
AU - Fan, Jian Bing
AU - Klotzle, Brandy
AU - Mahmoudi, Mohammad Jafar
AU - Ebrahimian, Mohammad Jafar
AU - Chelich, Noori
AU - Taghiabadi, Ehsan
AU - Kamyab, Kambiz
AU - Boileau, Catherine
AU - Paisan-Ruiz, Coro
AU - Ronaghi, Mostafa
AU - Elahi, Elahe
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Extracellular matrix
KW - LTBP2
KW - Marfan syndrome
KW - Microfibrils
KW - Weill-Marchesani syndrome
UR - http://www.scopus.com/inward/record.url?scp=84863869582&partnerID=8YFLogxK
U2 - 10.1002/humu.22105
DO - 10.1002/humu.22105
M3 - Article
C2 - 22539340
AN - SCOPUS:84863869582
SN - 1059-7794
VL - 33
SP - 1182
EP - 1187
JO - Human Mutation
JF - Human Mutation
IS - 8
ER -