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

NCT02859688 | Completed

• 1 other identifier: BRUNO AOI 2014
• Study Type: observational
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Epimutation

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

SRS patient

Genetic: pyrosequencing; Genetic: Methylome

father SRS patient

Genetic: pyrosequencing; Genetic: Methylome

control patient

Genetic: pyrosequencing; Genetic: Methylome

Interventions

pyrosequencing GENETIC

SRS patient; control patient; father SRS patient

Methylome GENETIC

SRS patient; control patient; father SRS patient

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1 patient SRS, the father of the patient SRS and 5 control patients : healthy men, age-matched

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU Dijon Bourgogne

Dijon, 21079, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood, sperm, saliva, skin biopsy

MeSH Terms

Interventions

High-Throughput Nucleotide Sequencing; Epigenome

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques; Genome; Genetic Structures; Genetic Phenomena

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 9, 2016
• Study Start: May 1, 2015
• Primary Completion: July 1, 2015
• Last Updated: August 9, 2016

Record last verified: 2016-07

Locations

FR (1)