Can Epimutations be Inherited? How to Manage Patients With Imprinting-related Diseases Who Wish to Become Parents

Completed

• Conditions: Epimutation
• Interventions: Genetic: pyrosequencing; Genetic: Methylome

• Registration Number: NCT02859688
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

Like genetic mutations, DNA methylation anomalies or epimutations can disrupt gene expression and lead to human diseases.

However, unlike genetic mutations, epimutations can in theory be reverted through developmental epigenetic re-programing, which should limit their transmission across generations. Following the request for a parental project of a patient diagnosed with Silver-Russell syndrome (SRS), and the availability of both somatic and spermatozoa DNA from the proband and his father, we had the exceptional opportunity to evaluate the question of inheritance of an epimutation. We provide here for the first time evidence for efficient reversion of a constitutive epimutation in the spermatozoa of an SRS patient, which has important implication for genetic counseling.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05
• Primary Completion: 2015-07
• Status Verified: 2016-07
• Study First Submitted: 2016-08-02
• Study First Submitted QC: 2016-08-04
• Last Update Submitted: 2016-08-04
• Study First Posted: 2016-08-09
• Last Update Posted: 2016-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 7

Inclusion Criteria

• Men who have been informed about the study
• Patients over 18 years old
• Fertile
• Matched for age with Silver Russel syndrome (SRS) patients

Exclusion Criteria

• Adults under guardianship
• Patients without national health insurance cover
• Patients with psychomotor development diseases or pulmonary, cardiac, renal or metabolic diseases (including type 1 and 2 diabetes before the pregnancy), inflammatory and systemic diseases, hypertension, neurological diseases, chronic hepatitis B or C, infection with human immunodeficiency virus (HIV).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
control patient	Methylome	-
father SRS patient	pyrosequencing	-
control patient	pyrosequencing	-
SRS patient	Methylome	-
SRS patient	pyrosequencing	-
father SRS patient	Methylome	-

Primary Outcome Measures

Name	Time	Method
Analysis of levels of methylation of deoxyribonucleic acid (DNA) measured by cloning/ sequencing and/or pyrosequencing for genes susceptible to imprinting (GSI)	Through the study completion up to 1 month

Trial Locations

Locations (1)

CHU Dijon Bourgogne; 🇫🇷 Dijon, France