Clinical Trial: Modifying Genes in Neurofibromatosis 1

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Observational

Official Title: Study of the Neurofibromatosis 1 Expression: Identification of the Modifying Genes

Brief Summary: Thanks to the investigators previous study the investigators demonstrated the influence of modifying genes in the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009; 18 (15) :2768-78). Indeed, analysis of the intra-and inter-family variability performed using the investigators phenotype/genotype database demonstrated a strong genetic component for most clinical features. The investigators results suggest the involvement of genetic factors, not related to the NF1 gene, the modifiers. The objective of this project is to identify the modifiers involved in the variability of clinical expression of NF1. The investigators will focus in particular variants involved in the development and progression of neurofibromas.

Detailed Summary:

Neurofibromatosis 1(NF1) is a rare autosomal dominant disorder with an incidence of one birth out of 3000. NF1 gene is located in 17q11.2. The penetrance is near 100% by the age of 8 and the de novo mutations represent half the cases. The product of NF1 gene is neurofibromin, a protein controlling cellular differentiation and proliferation. Phenotypic expression is variable even in the same family. Neurofibromatosis 1 is characterized by café au lait spots, freckling of the folds, Lisch'nodules (hamartomas of iris) and multiple neurofibromas. Manifestations of neurofibromatosis 1 are pleiotropic, potentially severe and unpredictable. Morbidity and mortality associated to neurofibromatosis 1 are linked with complications, optic pathway gliomas, neurofibromas of the spine or of peripheral nerves, learning disabilities, scoliosis and bone abnormalities and vasculopathy. The investigators already demonstrated the existence of modifiers, genes modifying the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009;18(15):2768-78). Indeed, a quantitative analysis of inter and intrafamilial variability performed with the data of the investigators phenotype/genotype database showed a strong genetic component for most studied clinical traits with an estimated heritability from 44 and 45% for subcutaneous and plexiform neurofibromas, to 66% for small café au lait spots. The investigators also showed that the NF1 gene had minor effect in the phenotypic variability. The investigators results suggested the implication of genes non linked to NF1 gene. The identification of these variants called modifiers of the phenotype is possible thanks to the investigators vast collection of patients and its statistical power. The aim of the present study is to identify in the human genome genetic variants in the evolving pattern of the most frequent manifestation of neurofibromatosis 1, neurofibromas. The genetic association stu
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Identification of the genetic variants involved in variability of clinical expression of neurofibromatosis 1. [ Time Frame: 3 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: May 29, 2012
Date Started: May 2012
Date Completion: September 2015
Last Updated: June 13, 2014
Last Verified: June 2014