2012
DOI: 10.1038/nature11011
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Patterns and rates of exonic de novo mutations in autism spectrum disorders

Abstract: Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there i… Show more

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Cited by 1,612 publications
(1,573 citation statements)
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“…identified de novo variations in FOXP1 , GRIN2B , SCN1A , LAMC3, and rare inherited CNTNAP2 variations (De Rubeis et al., 2014; O'Roak et al., 2011). Three genes were found in ASD probands with two de novo variations in each of these genes: BRCA2 , FAT1, and KCNMA1 (Neale et al., 2012). These studies also found significant enrichment of de novo variations in five ASD candidate genes including STXBP1 , MEF2C , KIRREL3 , RELN, and TUBA1A (Neale et al., 2012).…”
Section: Reviewmentioning
confidence: 99%
See 1 more Smart Citation
“…identified de novo variations in FOXP1 , GRIN2B , SCN1A , LAMC3, and rare inherited CNTNAP2 variations (De Rubeis et al., 2014; O'Roak et al., 2011). Three genes were found in ASD probands with two de novo variations in each of these genes: BRCA2 , FAT1, and KCNMA1 (Neale et al., 2012). These studies also found significant enrichment of de novo variations in five ASD candidate genes including STXBP1 , MEF2C , KIRREL3 , RELN, and TUBA1A (Neale et al., 2012).…”
Section: Reviewmentioning
confidence: 99%
“…Three genes were found in ASD probands with two de novo variations in each of these genes: BRCA2 , FAT1, and KCNMA1 (Neale et al., 2012). These studies also found significant enrichment of de novo variations in five ASD candidate genes including STXBP1 , MEF2C , KIRREL3 , RELN, and TUBA1A (Neale et al., 2012). Likewise, a region of chromosome 7q that includes the candidate genes RELN , FOXP2 , WNT2, and CADPS2 has been implicated in ASD (Liu & Takumi, 2014).…”
Section: Reviewmentioning
confidence: 99%
“…1,2 Recent studies have demonstrated that ASDs can be caused by rare, highly penetrant point mutations, deletions, duplications and larger chromosomal abnormalities that can either arise de novo or be inherited. [3][4][5][6][7][8][9] Known monogenic disorders account for 2-5% of syndromic cases; fragile X syndrome is usually the most common cause, followed by PTEN macrocephaly syndrome and tuberous sclerosis, each accounting for o1% of individuals with ASD. 1,10 Large copy number variants (CNVs) are found in 5-10% of autistic patients, especially in those with syndromic ASDs.…”
Section: Introductionmentioning
confidence: 99%
“…Those studies have reported hundreds of candidate genes with coding variants; however, for the vast majority of these candidates only a single mutation was identified in most genes (the Bn = 1 problem^). Such single-hit genes provide important data, but it is difficult to interpret whether they are truly associated with ASD without recurrent hits [3][4][5]176]. Sanders et al [4] developed a model suggesting that the likelihood of observing 2 nonsense/splice site de novo mutations in the same gene in probands is not by chance.…”
Section: De Novo Snvs In Asdmentioning
confidence: 99%