Abstracts

Rationale: Neurexin 1 (NRXN1) signalling pathway is critical for activity-dependent synaptic transmision and has been associated with autism and neurodevelopmental delay in a few instances. We report on a pair of fraternal twins with biallelic NRXN1 deletions identified by array CGH. Methods: Both children have autism and mental retardation. In addition, one child has epilepsy. Genomic DNA was isolated from blood for whole genome array CGH in both children. Genomic analysis was done by using the UCSC genome browser and Esembl ingenuity pathway was used for network analysis. Results: Whole-genome array CGH revealed a novel biallelic deletion of neurexin1 in both patients. One was a 282Kb deletion at band 2p16.3 in one allele and a smaller 174 Kb deletion on the second allele. Both mutations affect the promoter region and exons 1-5 in the alpha neurexin isoform that has a role in the calcium dependent release of neurotransmitters in the CNS Conclusions: Our report confirms that biallellic neurexin1 mutations in the alpha neurexin1 gene result in autism and developmental delay. NRXN1 mutations can cause mental retardation syndromes and epilepsy and broadens the range of phenotypes associated with this gene.