DE NOVO POINT MUTATIONS IN SUCH GENES COULD EXPLAIN THE ADVANCED PATERNAL AGE ASSOCIATON THAT HAS BEEN REPORTED FOR AUTISM

The Ethical Conduct of Clinical Research Involving Children (2004)
Board on Health Sciences Policy (HSP)
Arthur L. Beaudet, M.D.
News and Views


Nature Medicine - 13, 534 - 536 (2007)
doi:10.1038/nm0507-534
Autism: highly heritable but not inherited
Arthur L Beaudet
The author is in the Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. abeaudet@bcm.tmc.edu
Declaration: The author is at Baylor College of Medicine as Chair of the Department of Molecular and Human Genetics, which generates revenue by offering array CGH on a fee-for-service basis in collaboration with Athena Diagnostics using custom arrays from Agilent Technologies.




A couple of excerpts:




The genetic basis of autism is beginning to come to light. De novo mutations in gene copy number may have a big role.


Many of the lesions found in the Jacquemont et al.1 and Sebat et al.2 studies had not been previously reported, suggesting that not all regions of abnormality have been detected as yet. I would estimate that only half of the de novo mutations have been detected at present (Fig. 1). Higher density arrays focused at the level of single exons are likely to be very productive in identifying smaller abnormalities that may be immediately traceable to specific genes. It is clear that both CNVs and point mutations that often affect the same genes are making major contributions to the etiology of autism. Technically, it is easier to screen for CNVs than to sequence the entire genome to discover point mutations. De novo point mutations in such genes could explain the advanced paternal age association that has been reported for autism13. There is no evidence, however, that the risk of a de novo CNV is related to the age of either parent.



Could de novo CNVs and point mutations explain the whole of autism? Probably not, because one would expect more frequent parent-to-child transmission than is observed for mutations of strong effect, since many individuals with autism reproduce, especially the more mildly affected Asperger patients. In addition, the male predominance would remain unexplained, because these mutations generally affect both sexes about equally, and the 'unknown' residual group of patients is predominantly male (Fig. 1).



autism