Autism Spectrum Disorders (ASDs) are common, heritable neurobiologic conditions of unknown etiology confounded by significant clinical and genetic heterogeneity. We evaluated a broad categorization of phenotypic traits (or phenome) for 100 subjects with ADI-R/ADOS-G confirmed idiopathic ASD undergoing 1Mb BAC array-CGH. Array-CGH uncovered 9 different pathogenic copy number variants (pCNVs) in 9/100 ASD subjects having complex phenotypes (ASD± intellectual disability (ID; IQ<70)) and/or physical anomalies), normal karyotype, Fragile X analysis and comprehensive evaluation by a Clinical Geneticist. Unique pCNVs in our cohort included del(5)(p15.2p15.31) (2.4Mb), del(3)(p24.3) (0.1 Mb) and dup(18)(p11.3)(0.9 Mb). Five pCNVs were recurrent in our cohort or were previously described in subjects with ASD±ID: (dup(7)(q11.23)(1.5 Mb); del(2)(p15p16.1) (6.1 Mb and 7.9 Mb); del(14)(q11.2) (0.7 Mb) and dup(15)(q11q13) (10 Mb), including del(X)(p11.22) (470 Kb) in 2 autistic brothers. Male: female distribution in subjects with pCNVs was reduced to 1.25:1 from 3.2:1 in the original cohort. We stratified our study population according to a broad spectrum of clinical features and correlated specific phenotypes with respect to CNV load and pathogenicity. Our findings indicate increased prevalence of pCNVs in subjects with microcephaly (<2nd %; n=2 of 4 ASD subjects with microcephaly; p=0.04), and ID (n=9 of 64 subjects with ASD and ID; p=0.02). Interestingly, in the absence of ID co-morbidity with an ASD, no pCNVs were found. The relationship between parental ages at delivery and CNV load and pathogenicity was also explored.
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