A new study reports an increasing trend in the number of prenatal genetic tests to detect spontaneous mutations that can cause conditions such as Rett syndrome.
Genetic diseases are caused by mutations. Sometimes, these mutations are inherited from one or both parents, but at other times, the mutations occur spontaneously. These are called de novo mutations.
De novo mutations are rare — usually only about one per 10 million nucleotides (the “letters” that encode genetic information) when DNA is being copied. However, even such rare events can add up; this amounts to around 60 mutations per newly formed embryo. Most, if not all, of these mutations have little to no effect, but others, such as mutations in the MECP2 gene, can cause diseases such as Rett syndrome.
In the study, researchers examined the trend of using molecular tests to screen for de novo mutations during pregnancies. This involves getting a sample of amniotic fluid and then testing the fetus’ DNA for the presence of mutations by sequencing all or part of the DNA.
The researchers found that the frequency of testing for de novo mutations at their center in Israel increased substantially over the past 10 years: only three such procedures were done in 2007, compared to 24 in 2017.
Of the pregnancies in which a de novo mutation was identified, Rett syndrome was the most commonly diagnosed disease.
In three cases, the same mutation was found in back-to-back pregnancies, including one case where the mutation was linked to Rett syndrome. This suggests that these mutations weren’t actually de novo mutations. Instead, they were probably the result of germinal mosaicism, which is when there are mutations in a person’s germ cells (eggs or sperm) but not in the rest of their body.
Because these mutations are specific to a selected group of cells, they often aren’t detected in tests that look at blood cells, and germinal mosaicism is one of the reasons it can be advisable to do these types of genetic tests for subsequent pregnancies after a “spontaneous” mutation is found in one.
Researchers are hopeful that this trend is indicative of increased awareness about the importance of testing for rare genetic diseases such as Rett syndrome.
“Taken together, the growing number of prenatal diagnoses for de novo mutations reflects the growing understanding that such mutations contribute a significant portion of morbidity due to genetic diseases in the general population,” researchers said.