PMC:4067558 / 21371-23038 JSONTXT

{"project":"2_test","denotations":[{"id":"24768552-20004760-2047126","span":{"begin":837,"end":839},"obj":"20004760"}],"text":"Pathogenic CNVs included well-characterized highly penetrant disorders associated with de novo CNVs, such as Phelan-McDermid syndrome (MIM 606232, 22q13.3 deletion including SHANK3 [MIM 606230]), Smith-Magenis syndrome (MIM 182290, 17p11.2 deletion including RAI1 [MIM 607642]), Kleefstra syndrome (MIM 610253, 9q34.3 deletion including EHMT1 [MIM 607001]), Williams syndrome (MIM 194050, 7q11.23 deletion), and large chromosomal abnormalities (Figure 2A; Table S7B). Recurrent deleterious CNVs mediated by segmental duplications affecting 12 distinct regions were identified in 44 individuals. For example, two unrelated males were found to harbor Xq28 duplications (MIM 300815), one de novo and one maternal, corresponding to a ∼0.3 Mb segmental-duplication-mediated gain (153.2–153.5 Mb), which was previously reported in X-linked ID.42 GDI1 (MIM 300104), mutations of which are linked to ID, is the most likely gene involved (Figure S8). Thus, our findings implicate abnormal GDI1 dosage in ASD. Interestingly, one AGP proband with the duplication had autism and a normal IQ, whereas the second had a borderline IQ (72) (see Table S8 for phenotype information of all affected subjects with pathogenic CNVs). Some other findings include a 1.7 Mb de novo deletion encompassing ARID1B (MIM 614556), recently implicated in ID and Coffin-Siris syndrome (MIM 135900), and a small maternally inherited intragenic deletion of HDAC4 (MIM 605314), involved in brachydactyly-mental-retardation syndrome (MIM 600430; Figure S7). Although many 2q37 deletions have been described in ASD, the deletion found in our proband directly implicates HDAC4 haploinsufficiency in autism."}