Mutation of IGFBP7 Causes Upregulation of BRAF/MEK/ERK Pathway and Familial Retinal Arterial Macroaneurysms

被引：37

作者：

Abu-Safieh, Leen ^{[1
]}

Abboud, Emad B. ^{[2
]}

Alkuraya, Hisham ^{[1
,2
]}

Shamseldin, Hanan ^{[1
]}

Al-Enzi, Shamsa ^{[1
]}

Al-Abdi, Lama ^{[1
]}

Hashem, Mais ^{[1
]}

Colak, Dilek ^{[3
]}

Jarallah, Abdullah ^{[4
]}

Ahmad, Hala ^{[5
]}

Bobis, Steve ^{[5
]}

Nemer, Georges ^{[6
]}

Bitar, Fadi ^{[7
]}

Alkuraya, Fowzan S. ^{[1
,8
,9
]}

机构：

[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[2] King Khalid Eye Specialist Hosp, Vitreoretinal Div, Riyadh 11462, Saudi Arabia

[3] King Faisal Specialist Hosp & Res Ctr, Dept Biostat Epidemiol & Comp, Riyadh 11211, Saudi Arabia

[4] King Khalid Univ Hosp & Coll Med, Dept Cardiac Sci, Riyadh 11462, Saudi Arabia

[5] King Faisal Specialist Hosp & Res Ctr, Dept Comparat Med, Riyadh 11211, Saudi Arabia

[6] Amer Univ Beirut, Dept Biochem & Mol Genet, Beirut 11072020, Lebanon

[7] Amer Univ Beirut, Dept Pediat, Beirut 11072020, Lebanon

[8] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh 11533, Saudi Arabia

[9] King Khalid Univ Hosp & Coll Med, Dept Pediat, Riyadh 11462, Saudi Arabia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2011年 / 89卷 / 02期

关键词：

GROWTH; IDENTIFICATION; SENESCENCE; APOPTOSIS; PROTEIN; CELLS; BRAF;

D O I：

10.1016/j.ajhg.2011.07.010

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Insulin-like growth factor binding proteins (IGFBPs) play important physiological functions through the modulation of IGF signaling as well as IGF-independent mechanisms. Despite the established role of IGFs in development, a similar role for the seven known IGFBPs has not been established in humans. Here, we show that an autosomal-recessive syndrome that consists of progressive retinal arterial macroaneurysms and supravalvular pulmonic stenosis is caused by mutation of IGFBP7. Consistent with the recently established inhibitory role of IGFBP7 on BRAF signaling, the BRAF/MEK/ERK pathway is upregulated in these patients, which may explain why the cardiac phenotype overlaps with other disorders characterized by germline mutations in this pathway. The retinal phenotype appears to be mediated by a role in vascular endothelium, where IGFBP7 is highly expressed.

引用

页码：313 / 319

页数：7

共 22 条

[21]

ZENKER M, 2008, NOONAN SYNDROME RELA

[22] IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis [J].

Zhu, Weidong ;

Shiojima, Ichiro ;

Ito, Yuzuru ;

Li, Zhi ;

Ikeda, Hiroyuki ;

Yoshida, Masashi ;

Naito, Atsuhiko T. ;

Nishi, Jun-ichiro ;

Ueno, Hiroo ;

Umezawa, Akihiro ;

Minamino, Tohru ;

Nagai, Toshio ;

Kikuchi, Akira ;

Asashima, Makoto ;

Komuro, Issei .

NATURE, 2008, 454 (7202) :345-U51

← 1 2 3 →