In ~10% of patients with autism, genome sequencing reveals multiple
de novo and disruptive mutations in different genes and
their regulatory DNA. For example, (A) a child from SSC family 13122 inherits
two large deletions affecting putative regulatory regions of autism risk genes
NTM and RBFOX1. (B) Similarly, a child in
SSC family 11709 inherits three different deletions with two affecting putative
regulatory regions of the autism risk genes ARID1B and
SCN2A. (C) Examination of families with multiple affected
individuals frequently finds that a genetic risk variant segregates to only one
of the two children or that different affected individuals each carry a
different risk variant. For example, in MSSNG multiplex family 2–0006
[34], one autistic offspring carries
a de novo loss-of- function event in STXBP1
while the other affected male sibling carries a maternally inherited
loss-of-function event in UBE3A. Panels (A) and (B) are adapted
from Turner et al. 2016 [17]. MSSNG
family 2–0006 was studied in Yuen et al. 2015 [34].