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open 11 no This work was supported by grants from Fondazione Banco di Sardegna (FBS) (1175/2009.0470) to GD, from Associazione Italiana Studio Malformazioni (ASM) (2010) to PZ, from the Kyulan Family Foundation to EBa and from CINECA (computational resources to EBa). Partly supported also by grants from Fondo per la Ricerca Locale (ex 60%), Università di Cagliari, to PZ and from Fondo per la Ricerca Fondamentale Orientata (ex quota 60%), University of Bologna, to EM. Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by high heritability. It is known that genetic factors contribute to ASD pathogenesis. In particular, copy number variants (CNVs) are involved in ASD susceptibility and can affect gene expression regulation. 2p11.2 microdeletions encompassing ELMOD3, CAPG and SH2D6 genes have been described in four unrelated ASD families. The present study revealed that this microdeletion is responsible for the production of a chimeric transcript generated from the fusion between ELMOD3 and SH2D6. The identified transcript showed significantly higher expression levels in subjects carrying the deletion compared to control subjects, suggesting that it is not subjected to nonsense-mediated decay and might encode for a chimeric protein. In conclusion, this study suggests the possible involvement of this gene fusion, together with the other previously identified variants, in ASD. open Loi E.; Moi L.; Blois S.; Bacchelli E.; Vega Benedetti A.F.; Cameli C.; Fadda R.; Maestrini E.; Carta M.; Doneddu G.; Zavattari P. Loi E.; Moi L.; Blois S.; Bacchelli E.; Vega Benedetti A.F.; Cameli C.; Fadda R.; Maestrini E.; Carta M.; Doneddu G.; Zavattari P.

Chromosome 15q13.3 recurrent microdeletions are causally associated with a wide range of phenotypes, including autism spectrum disorder (ASD), seizures, intellectual disability, and other psychiatric conditions. Whether the reciprocal microduplication is pathogenic is less certain. CHRNA7, encoding for the alpha7 subunit of the neuronal nicotinic acetylcholine receptor, is considered the likely culprit gene in mediating neurological phenotypes in 15q13.3 deletion cases. To assess if CHRNA7 rare variants confer risk to ASD, we performed copy number variant analysis and Sanger sequencing of the CHRNA7 coding sequence in a sample of 135 ASD cases. Sequence variation in this gene remains largely unexplored, given the existence of a fusion gene, CHRFAM7A, which includes a nearly identical partial duplication of CHRNA7. Hence, attempts to sequence coding exons must distinguish between CHRNA7 and CHRFAM7A, making next-generation sequencing approaches unreliable for this purpose. A CHRNA7 microduplication was detected in a patient with autism and moderate cognitive impairment; while no rare damaging variants were identified in the coding region, we detected rare variants in the promoter region, previously described to functionally reduce transcription. This study represents the first sequence variant analysis of CHRNA7 in a sample of idiopathic autism.