De novo mutation

What is a de novo mutation?

A de novo mutation is a mutation that appears in a family for the first time, with neither the parents nor the grandparents showing the genetic alteration. These mutations occur in a germ cell of one of the parents (egg or sperm) or directly in the zygote (the fertilized egg).

When a sporadic case of a hereditary genetic disease is identified (an affected person is born in a family with no history of the disease), it can be difficult to determine the inheritance pattern: It could be a recessive disease for which both parents are carriers but are not affected (a second child would have a 25% probability of also being affected), or it could be a de novo mutation (in this case, the probability that a second child is affected is usually much lower and depends on the number of gametes affected by the new mutation). If an affected individual with a de novo mutation has children, that mutation will be transmitted following the corresponding inheritance pattern of that particular disease. In fact, all mutations we inherit from our parents were at some point de novo mutations that had appeared in some of our ancestors.

Some synonyms for de novo mutations are new genetic mutations, spontaneous mutations, or sporadic mutations.

> Genetic diseases and de novo mutations:

De novo mutations are not particularly common. Nevertheless, there are genes which show increased mutation rates, be it because of their size (as it is more probable that a mutation occurs in a larger gene than in a smaller one) or because they are situated in the so-called mutational hotspots of the genome, which are sites with observed high mutation rates.

Some genetic diseases that display a significant number of cases caused by de novo mutations are:

• Achondroplasia
• Duchenne and Becker muscular dystrophy
• Charcot-Marie-Tooth disease
• Hemophilia
• Neurofibromatosis
• Osteogenesis imperfecta
• Retinitis pigmentosa
• Marfan syndrome