Genotype and Phenotype Analysis of Monozygotic Twins Concordant for Autism

Autism is a neurodevelopmental disorder which manifests as deficits in social interaction, communication, and in stereotyped or repetitive behaviors before three years of age. The presence of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) detected by microarray can lead to more information regarding the etiology of autism. Six pairs of monozygotic twins affected with autism enrolled in the University of California, Irvine Autism Research Project were analyzed using a microarray chip for CNVs and SNP concordance in relation to autism severity. The data on all of the twin pairs were consistent with monozygosity. However, each pair was discordant for a small number of SNPs; the lowest concordance percentage was 99.1 for one twin pair. CNVs were determined using three parameters: >20 markers, >100kb, and no more than 60% overlap with known variants; >10 markers, >50kb, and no more than 60% overlap; >20 markers, >10kb, and 0% overlap. One twin pair was discordant for an unbalanced (2,7) translocation which involved an 82.5 Mb duplication of 2p and a 4.1 Mb loss on 7p. One gene of significance in the duplicated region is Neurexin 1 (NRXN1). Another twin pair was discordant for a duplication which involves dopamine beta-hydroxylase (DBH). Another twin pair was concordant for a duplication involving synaptic nuclear envelope 2 (SYNE2) and estrogen receptor beta 2 (ESR2). Importantly, monozygotic twins, which were previously thought to be genetically identical, are not truly 100% identical.