A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2020 | Number 1, Volume 34

Mutations in father’s sperm may offer clues about odds of having a second child with ASD

Analyzing the sperm of fathers who already have a child with an autism spectrum disorder (ASD) may help families to better understand the odds of future children having the condition, a new study suggests. 

Research indicates that as many as 30 percent of cases of ASD are caused by de novo mutations, which are mutations occurring spontaneously in a parent’s sperm or eggs at conception. Martin Breuss and colleagues note that “de novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception.” 

In the new study, Breuss and his team analyzed the sperm of eight fathers who were parents of children with ASD, looking for mosaicism—that is, the presence of two or more genetically different sets of cells. Using a technique called deep whole genome sequencing, they detected variants in the children that were matched only in the fathers’ sperm. 

“While medical textbooks teach us that every cell in the body has an identical copy of DNA,” Breuss says, “this is fundamentally not correct. Mutations occur every time a cell divides, so no two cells in the body are genetically identical.” He adds, “If a mutation occurs early in development, then it will be shared by many cells within the body. But if a mutation happens just in sperm, then it can show up in a future child but not cause any disease in the father.” 

The researchers determined that mutations were present in up to 15 percent of the fathers’ sperm cells. This information could not be determined through other means, such as blood samples. 

Breuss and colleagues say it may be possible to develop a clinical test that will help fathers of children with ASD determine their odds of having another child with the condition. In addition, they say, the test may benefit men who have not yet had children but want to know their odds of having a child with ASD.


“Autism risk in offspring can be assessed through quantification of male sperm mosaicism,” Martin W. Breuss, Danny Antaki, Renee D. George, Morgan Kleiber, Kiely N. James, Laurel L. Ball, Oanh Hong, Ileena Mitra, Xiaoxu Yang, Sara A. Wirth, Jing Gu, Camila A. B. Garcia, Madhusudan Gujral, William M. Brandler, Damir Musaev, An Nguyen, Jennifer McEvoy-Venneri, Renatta Knox, Evan Sticca, Martha Cristina Cancino Botello, Javiera Uribe Fenner, Maria Cárcel Pérez, Maria Arranz, Andrea B. Moffitt, Zihua Wang, Amaia Hervás, Orrin Devinsky, Melissa Gymrek, Jonathan Sebat, and Joseph G. Gleeson, Nature Medicine, December 23, 2019 (online). Address: Joseph Gleeson, Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, [email protected]


“Measuring mutations in sperm may reveal risk for autism in future children,” Medical Xpress, December 23, 2019.