NDLI: Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14

Content Provider	PubMed Central
Author	Letteboer, Tom G. W. Michael, Benzinou Merrick, Christopher B. Quigley, David A. Zhau, Kechen Kim, Il-jin To, Minh D. Jablons, David M. Amstel, Johannes K. P. Van Westermann, Cornelius J. J. Giraud, Sophie Sophie, Dupuis-girod Lesca, Gaetan Berg, Jonathan H. Balmain, Allan Akhurst, Rosemary J.
Copyright Year	2015
Abstract	HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018–1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75–0.9, P < 1 × 10−12), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT therapy.
Related Links	http://dx.doi.org/10.3389/fgene.2015.00067
Starting Page	67
File Format	PDF
ISSN	16648021
e-ISSN	16648021
Journal	Frontiers in Genetics
Volume Number	6
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2015-03-01
Access Restriction	Open
Rights Holder	Frontiers Media S.A.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Medicine Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14

The prevalence of hereditary hemorrhagic telangiectasia in Juvenile Polyposis syndrome patients with SMAD4 mutations

Imaging of Hereditary Hemorrhagic Telangiectasia

Pulmonary Arteriovenous Malformation as the Initial Manifestation of Hereditary Hemorrhagic Telangiectasia

Case Report: Clinical characteristics and genetic analysis of two patients with hereditary hemorrhagic telangiectasia

Pulmonary arteriovenous malformation with unexplained cyanosis as the first presentation of hereditary haemorrhagic telangiectasia, case report, and literature review

Case report: Pulmonary arterial hypertension in ENG-related hereditary hemorrhagic telangiectasia

Pulmonary Arteriovenous Malformation in a Young Patient with Suspected Hereditary Hemorrhagic Telangiectasia: A Case Report

Predictors of mortality in patients with hereditary hemorrhagic telangiectasia

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14

Similar Documents

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14

The prevalence of hereditary hemorrhagic telangiectasia in Juvenile Polyposis syndrome patients with SMAD4 mutations

Imaging of Hereditary Hemorrhagic Telangiectasia

Pulmonary Arteriovenous Malformation as the Initial Manifestation of Hereditary Hemorrhagic Telangiectasia

Case Report: Clinical characteristics and genetic analysis of two patients with hereditary hemorrhagic telangiectasia

Pulmonary arteriovenous malformation with unexplained cyanosis as the first presentation of hereditary haemorrhagic telangiectasia, case report, and literature review

Case report: Pulmonary arterial hypertension in ENG-related hereditary hemorrhagic telangiectasia

Pulmonary Arteriovenous Malformation in a Young Patient with Suspected Hereditary Hemorrhagic Telangiectasia: A Case Report

Predictors of mortality in patients with hereditary hemorrhagic telangiectasia

Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14