Which statement best describes a de novo mutation and its impact on recurrence risk when there is no family history?

• A. A de novo mutation is a variant inherited from a parent.
• B. A de novo mutation is a common variant in the population.
• C. A de novo mutation is a new pathogenic variant arising in the affected individual; recurrence risk for siblings is typically low, though parental germline mosaicism can raise it.
• D. A de novo mutation cannot cause disease.

Answer: (C)

De novo mutations are new genetic changes that arise in the affected individual and are not present in the parents’ germline. When there’s no family history, this explains why the child is affected despite parents showing no signs, and it underpins why recurrence in siblings is typically low. Yet there’s a notable caveat: parental germline mosaicism can mean some of a parent’s gametes carry the mutation, modestly increasing the chance of another affected child. Importantly, de novo mutations can be pathogenic and cause disease. They are not inherited from a parent, they are not common population variants, and they can indeed lead to disease when they occur.