Similarly, with the development of high-throughput sequencing, hundreds of genes can be sequenced for RVs in ASDs. In the following sections,
we will review RVs associated with ASDs, including genetic conditions, CNVs, and mutations (Table I). Table I. Multiple rare variants in autism spectrum disorders (ASDs). While epidemiologically rigorous studies have yet to be carried out, there are reasonable estimates for the prevalence of some of the genetic contributors to ASDs. Some of the more common ones … Genetic conditions associated with ASDs A variety of genetic conditions, of which most can be syndromic (ie, associated with recognizable clinical signs, including Inhibitors,research,lifescience,medical dysmorphic, metabolic, or neurological features) can present with ASDs. These include 15qll-13 duplications, 22qll deletion/DiGcorgc syndrome, 22qll duplication syndrome, 22ql3 deletion syndrome, adenylosuccinate lyase Inhibitors,research,lifescience,medical deficiency, Angelman syndrome (AS), Cohen syndrome, Down syndrome, Fragile X syndrome, MA’CP2-rclatcd disorders, neurofibromatosis, untreated phenylketonuria, Potocki-Lupski syndrome, Prader-Willi syndrome (PWS), FT’/P450 inhibitor screening library tW-associated syndromes, San Filippo syndrome, Smith-Magenis syndrome, SmithLemli-Opitz
syndrome, Sotos syndrome, Inhibitors,research,lifescience,medical tuberous sclerosis, and Williams syndrome.13-17 For individuals with these syndromes, a proportion of cases can have an ASD diagnosis18,19 and for some of these conditions, there have been examples of individuals identified with a primary diagnosis of ASD, and only later was the syndrome identified (that is to say that a proportion of individuals with assessed with idiopathic ASDs may have some of these conditions, perhaps without a typical syndromal presentation). In some cases, the genetics of Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical the ASD-associated syndrome
is well understood. Fragile X syndrome (FXS), caused by a trinucleotide repeat expansion in the fragile X mental retardation 1 (FMRl) gene at Xq27.3, is among the most common syndromes associated with ASDs. Among individuals with FXS, ASD symptoms occur in one quarter to one third of subjects,20,21 while the prevalence of FXS is estimated to be 2% among individuals identified with an ASD. AS and PWS, as well as 15qll-13 duplications, collectively are also common ASD-associated syndromes, of which each has different molecular etiology.15,22,23 Etomidate Rett syndrome, listed among the PDDs in DSM-IV, is caused by mutation in the gene encoding methyl -CpG-binding protein-2 (MECP2) and a proportion of girls identified with an ASD are found to have Rett syndrome.24 Novel CNVs associated with ASDs identified by genome-wide scanning Novel CNVs in ASDs Whole genome scans for CNVs use genome-wide arraybased methods to search for deletions and duplications. ‘ITtiis approach complements karyotyping and targeted methods such as fluorescence in situ hybridization (FISH).