Dataset Information

Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms.

ABSTRACT: 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.

SUBMITTER: Abu-Safieh L

PROVIDER: S-EPMC3155176 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms.

Abu-Safieh Leen L Abboud Emad B EB Alkuraya Hisham H Shamseldin Hanan H Al-Enzi Shamsa S Al-Abdi Lama L Hashem Mais M Colak Dilek D Jarallah Abdullah A Ahmad Hala H Bobis Steve S Nemer Georges G Bitar Fadi F Alkuraya Fowzan S FS

American journal of human genetics 20110801 2

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 t ...[more]

PMID: 21835307

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Project description:Retinal arterial macroaneurysms (RAMs) develop as outpouchings of the arterial wall that is weakened by arteriosclerosis. The traditional treatment of RAMs comprises observation, focal laser photocoagulation, or surgery. Recently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has been announced as an effective therapy for fovea-threatening RAMs and quickly improve visual acuity and central retinal thickness (CRT).In the retrospective series, medical charts and ocular images of 24 patients diagnosed as having RAM between May 2011 and November 2018 in our facility were reviewed to delineate clinical manifestations and visual prognosis in RAM patients receiving different treatment modalities. Twenty-four patients (25 eyes; 11 men and 13 women) were enrolled, and one eye with comorbidity of branch retinal vein occlusion was excluded. The mean age of the patients was 69.00?±?13.45 years. Fourteen patients (58.33%) had a history of hypertension, and 17 patients (70.83%) were aged >?60 years. Furthermore, patients with fovea-threatening RAMs presented with either hypertension or were aged >?60 years.Eyes with fovea involvement (n?=?18) were analyzed and separated into two groups according to their treatment modalities: those receiving anti-VEGF intravitreal injections (n?=?13) and observation only (n?=?5). The baseline visual acuity revealed no significant difference in the two groups. In patients receiving anti-VEGF intravitreal injections, a significantly better visual acuity was detected after anti-VEGF intravitreal injections than the baseline visual acuity (logMAR, 0.78?±?0.51 vs 1.52?±?0.48, P?<?.001), and CRT significantly improved (505.50?±?159.26??m vs 243.60?±?60.17??m, P?=?.001). Patients receiving anti-VEGF intravitreal injections also revealed better final visual acuity than those in the observation group (logMAR, 0.78?±?0.51 vs 1.34?±?0.48, P?=?.04).A systematic work-up for hypertension and arteriosclerotic disease could be considered the recommended procedure once RAM has been diagnosed. With better final visual acuity, significant visual improvements, and fast reduction of CRT observed in patients with fovea-threatening RAMs receiving anti-VEGF intravitreal injections, intravitreal anti-VEGF was considered an effective therapy for complicated RAM. During the follow-up period, the majority of RAM eyes had good maintenance of visual function even with foveal complications.

Dataset Information

Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms.

Publications

Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms.

Similar Datasets

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