Molecular Aspects of Preimplantation Genetic Diagnosis for NF1 (NF1)

Evaluation of Preimplantation Genetic Diagnosis for Neurofibromatosis Type 1 (NF1), Emphasizing on the Molecular Aspects

Neurofibromatosis 1 (NF1) is a multisystem disorders characterized by skin abnormalities, such as café-au-lait spots and neurofibromas, learning disabilities, skeletal anomalies and vascular complications. Experience learns that this disorder is a great burden for patients. NF1 is an autosomal dominant disorder with 50% risk of transmission. The penetrance is nearly 100%, but the expression varies greatly even within families, which makes it nearly impossible to predict severity in offspring. Preimplantation genetic diagnosis (PGD) is a reproductive option for couples at risk of transmitting NF1 to their offspring. We perform a retrospective and observational multicentric study in the Maastricht University Medical Center, the University Hospital of Brussel and Strasbourg University Hospital. Our specific (and first) goal is to evaluate the molecular aspects of PGD for NF1 in an international cohort of couples requesting PGD for NF1.

About 50% of the patients with NF1 have a de novo mutation that can complicate development of a PGD test. Earlier studies from 1990 and 1992 have shown that de novo NF1 mutations usually occur on the paternal allele. We want to confirm these findings with collected data from our cohort. The high incidence of de novo mutations results in a higher chance of finding mosaicism in patients or their parents. As a result of this, it can become apparent during PGD test preparation that PGD treatment is no longer possible or indicated. The investigators will evaluate these aspects of PGD for NF1 in our cohort.

They are also interested, as a second goal, in other aspects of PGD treatment for NF1, such as the success rate in thier cohort. They expect the success rate to be the same as for other autosomal dominant disorders

Study Overview

• Status: Recruiting
• Conditions: Neurofibromatosis Type 1

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Céline MOUTOU, MD; Phone Number: 33 3.69.55.34.65; Email: celine.moutou@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67091
    • Recruiting
    • Service Laboratoire de Diagnostic Génétique - Hôpitaux Universitaires de Strasbourg
    • Contact: Céline MOUTOU, MD; Phone Number: 33 3.69.55.34.65; Email: celine.moutou@chru-strasbourg.fr
    • Sub-Investigator: Julia LAUER ZILLHARDT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

- Major subjects (≥18 years old) who have been treated at the HUS for a preimplantation diagnosis request for type 1 neurofibromatosis (confirmed by a molecular molecular analysis) and who have benefited from preliminary analyzes, between 01/01/2004 and 30/06 / 2021

Description

Inclusion criteria:

• Major subjects (≥18 years old)
• Couples who have been treated at the HUS for a preimplantation diagnosis request for type 1 neurofibromatosis (confirmed by a molecular molecular analysis) and who have benefited from preliminary analyzes, between 01/01/2004 and 30/06 / 2021
• Couple who, after receiving information, did not express their opposition to the reuse of their data for the purposes of this research

Exclusion criteria:

• Couples who expressed their opposition to participating in the study
• Subject under guardianship, curatorship or safeguard of justice

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Study of the molecular aspects of PGD for NF1 in a large European cohort.	Files analysed retrospectively from from January 1, 2004 to June 30, 2021 will be examined]

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2021
• Last Update Submitted That Met QC Criteria: November 24, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Neurofibromatosis Type 1; NF1; Mosaicism; Preimplantation genetic diagnosis; De novo mutation; Molecular test
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
• Other Study ID Numbers: 8374

Drug and device information, study documents

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