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

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

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.

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).