Clinical and Molecular Characterization of Cerebral Proliferative Vasculopathy (VPCA)

As principal objective, the study aims to:

1. Describe the spectrum and evaluate the frequency of angiodysplasia of the nevrax;
2. Establish the physiopathological basis of Fowler's syndrome;
3. Identify FLVCR2 partners and the signaling pathways involved;
4. Test new candidate genes: GPR124 and possible partners of FLVCR2.

As second objective, the study aims to:

• perform phenotype / genotype correlation if necessary;
• and propose a prenatal diagnosis in families with identified mutations.

Study Overview

• Status: Completed
• Conditions: Proliferative Vasculopathy

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• France
  • Paris, France, 75006
    • Hôpital Necker Enfants Malades, APHP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Intrauterine fetal death and those from termination of pregnancy for fetal abnormality.

Description

Inclusion Criteria:

• Angiodysplasia restricted to central nervous system with or without glomerular vasculopathy.
• Informed consent signed.

Exclusion Criteria:

• Vascular malformations not confined to the nevrax.
• No signature of consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphological analysis	Morphological analysis : characterisation of cellular lesions by immunolabelling with endothelial markers such as CD34 and CD31, pericytic markers (smooth muscle actin and proteoglycan NG2) and astrocytic markers (GFAP)	throughout the study: 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of novel disease	Identification of novel disease causing genes in addition to FLVCR2 by whole exome sequencing. Fetus with clinical VPCA and no FLVCR2 mutation found by Sanger sequencing, will be studied by whole exome sequencing in order to find mutation in other genes that could explain the phenotype.	throughout the study: 36 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Tania Attié-Bitach, MD, PhD, Hôpital Necker Enfants Malades, APHP

Publications and helpful links

General Publications

• Thomas S, Encha-Razavi F, Devisme L, Etchevers H, Bessieres-Grattagliano B, Goudefroye G, Elkhartoufi N, Pateau E, Ichkou A, Bonniere M, Marcorelle P, Parent P, Manouvrier S, Holder M, Laquerriere A, Loeuillet L, Roume J, Martinovic J, Mougou-Zerelli S, Gonzales M, Meyer V, Wessner M, Feysot CB, Nitschke P, Leticee N, Munnich A, Lyonnet S, Wookey P, Gyapay G, Foliguet B, Vekemans M, Attie-Bitach T. High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy. Hum Mutat. 2010 Oct;31(10):1134-41. doi: 10.1002/humu.21329.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2013
• Primary Completion (Actual): March 9, 2015
• Study Completion (Actual): October 6, 2016

Study Registration Dates

• First Submitted: May 2, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Fowler syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases
• Other Study ID Numbers: NI11031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No