Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autismMeyer, Kacie J.a; Axelsen, Michael S.b; Sheffield, Val C.c,d; Patil, Shivanand R.c; Wassink, Thomas H.bPsychiatric Genetics: June 2012 - Volume 22 - Issue 3 - p 137–140 doi: 10.1097/YPG.0b013e32834dc3f5 Brief Reports Abstract Author Information Autism is a neurodevelopmental disorder with a strong genetic component to susceptibility. In this study, we report the molecular characterization of an apparent de-novo 281 kb duplication of chromosome 2p25.3 in two male half-siblings with autism. The 2p25.3 duplication was first identified through a low-density microarray, validated with fluorescent in-situ hybridization, and duplication breakpoints were delineated using an Affymetrix 6.0 single-nucleotide polymorphism microarray. The fluorescent in-situ hybridization results validated the novel copy number variant and revealed the mother to be mosaic, with∼33% of her lymphoblast cells carrying the duplication. Therefore, the duplication was transmitted through the mechanism of germline mosaicism. In addition, duplication breakpoints were refined and showed that PXDN is fully duplicated, whereas seven exons of the terminal portion of the 25 exon gene MYT1L are within the duplicated region. MYT1L, a gene predominately expressed in the brain, has recently been linked with other neuropsychiatric illness such as schizophrenia and depression. Results from this study indicate that the 2p25.3 duplication disrupting PXDN and MYT1L is a potential autism-causing variant in the pedigree reported here and should receive further consideration as a candidate for autism. Departments of aMolecular Physiology and Biophysics bPsychiatry cPediatrics dHoward Hughes Medical Institute, University of Iowa, Iowa, USA Correspondence to Kacie J. Meyer, BD, Department of Molecular Physiology and Biophysics, University of Iowa, Interdisciplinary Genetics Program, 375 Newton Rd., 4181 MERF, Iowa City, Iowa 52242, USA Tel: +1 319 353 4488; fax: +1 319 353 3003; e-mail: email@example.com Received January 12, 2011 Accepted August 15, 2011 © 2012 Lippincott Williams & Wilkins, Inc.