The name is absent

Autism prodrome 45 of 89

de novo mutations - which could not be detected by standard linkage and association
gene mapping approaches. Statistical analysis of ASD family data has recently
suggested that a significant proportion of ASD cases may be the result of dominantly
acting de novo mutations that have a reduced penetrance in females (Zhao et al.,
2007). Further support for this idea comes from a growing list of single genetic
lesions, each of which seems to be largely sufficient to cause ASD. This includes
large cytogenetic abnormalities, copy number variations (CNVs) and single base
mutations. The high concordance rate in monozygotic twins and very low
concordance in dizygotic twins also fits with contribution of de novo mutations.

Chromosomal abnormalities, such as rearrangements, duplications and
deletions, have been identified in 6-7% of ASDs (Marshall et al., 2008). The most
frequent changes are duplications of 15q11-13 accounting for 1-2% of cases. Other
chromosomal abnormalities observed in multiple patients include deletions of 2q37,
7q31, 22q11.2 and 22q13.3 (Freitag, 2007; Vorstman et al., 2006). Recent studies,
using high-resolution microarray technologies, suggest that de novo CNVs accounts
for about 10-20% of ASD cases (Abrahams & Geschwind, 2008; Sebat et al., 2007).
CNVs are segments of DNA for which copy-number differences have been revealed
by comparison of two or more genomesand are too small to be identified using a
microscope (Feuk, Carson, & Scherer, 2006).The proportion of de novo CNVs was
found to be different between simplex families (7-10%), multiplex families (2-3%)
and non-ASD controls (1%) (Marshall et al., 2008; Sebat et al., 2007). Other
researchers have found that deletions and duplications of 16p11.2 account for around
1% of autism cases (Weiss et al., 2008). The most recent whole-genome CNV study
on a cohort of 859 ASD cases and 1,409 controls reported that several genes involved
in neuronal cell-adhesion or ubiquitin degradation are enriched with CNVs in ASD

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