A team of researchers led by Cold Spring Harbor Laboratory (CSHL) and Albert Einstein College of Medicine analyzed data on autism incidence and found a formerly unrecognized pattern. The pattern can be explained by assuming that spontaneous germ-line mutation is a major cause of the disorder. Parents, especially women, who acquire the mutation but do not display severe symptoms of the disorder, have a 50 percent likelihood of passing the mutation on to their children.
Spontaneous mutations are changes in a chromosome that modify genes. Germ-line mutations are newly acquired in a germ cell of a parent, and sometimes are transmitted to offspring at conception. Men and women are equally as likely to get hold of a spontaneous mutation that can cause autism, but autism is three times more likely in men, making women the more likely carriers of new mutations.
"The fact that germ-line mutations increase with age places older parents at a higher risk of having children with autism, explaining a pattern that has been recently observed," said CSHL co-author of the study Michael Wigler, Ph.D.
The model puts forward two important risk classes for families affected by autism. Low risk families give rise to sporadic autism, the more common form, by spontaneous germ-line mutation. The children, mostly female, who receive such a mutation, but do not exhibit the disorder, are the source of the high risk families.
The data show that the transmission pattern to boys in high risk families is often of a dominant pattern that may give an explanation for a quarter of autism. Although the data does not answer whether there is a gradation of lower risk, the model builds on recent CSHL findings that spontaneous mutation is frequent in sporadic autism and less frequent in children from high risk families.
Wigler suggests that "what we now know about spontaneous mutations and autism offers an alternative to traditional thinking about genetic disorders as purely heritable from a parent. This has implications for other disorders such as morbid obesity, schizophrenia, and congenital heart disease."
The paper, titled "A unified theory for sporadic and inherited autism," is published in the July 31, 2007 print edition of the Proceedings of the National Academy of Sciences.