TY - JOUR
T1 - Rare deletions at the neurexin 3 locus in autism spectrum disorder
AU - Vaags, Andrea K.
AU - Lionel, Anath C.
AU - Sato, Daisuke
AU - Goodenberger, McKinsey
AU - Stein, Quinn P.
AU - Curran, Sarah
AU - Ogilvie, Caroline
AU - Ahn, Joo Wook
AU - Drmic, Irene
AU - Senman, Lili
AU - Chrysler, Christina
AU - Thompson, Ann
AU - Russell, Carolyn
AU - Prasad, Aparna
AU - Walker, Susan
AU - Pinto, Dalila
AU - Marshall, Christian R.
AU - Stavropoulos, Dimitri J.
AU - Zwaigenbaum, Lonnie
AU - Fernandez, Bridget A.
AU - Fombonne, Eric
AU - Bolton, Patrick F.
AU - Collier, David A.
AU - Hodge, Jennelle C.
AU - Roberts, Wendy
AU - Szatmari, Peter
AU - Scherer, Stephen W.
N1 - Funding Information:
We thank the WTCCC and the SAGE (Study of Addiction: Genetics and Environment) consortium and A. Fiebig, A. Franke, and S. Schreiber at PopGen (University of Kiel, Kiel, Germany) and A. Stewart, R. McPherson, and R. Roberts of the University of Ottawa Heart Institute (University of Ottawa, Ottawa, Canada), for providing control data. This work was supported by The Centre for Applied Genomics, Genome Canada and the Ontario Genomics Institute, the Canadian Institutes for Health Research, the Canadian Institute for Advanced Research, the McLaughlin Centre, the Canada Foundation for Innovation, the Ontario Ministry of Research and Innovation, Autism Speaks, NeuroDevNet, and the Hospital for Sick Children Foundation. A.C.L. holds an Ontario graduate scholarship from the Ontario Ministry of Education and Training and a NeuroDevNet doctoral fellowship. S.W.S. holds the GlaxoSmithKline-CIHR chair in Genome Sciences at the University of Toronto and the Hospital for Sick Children.
PY - 2012/1/13
Y1 - 2012/1/13
N2 - The three members of the human neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3), encode neuronal adhesion proteins that have important roles in synapse development and function. In autism spectrum disorder (ASD), as well as in other neurodevelopmental conditions, rare exonic copy-number variants and/or point mutations have been identified in the NRXN1 and NRXN2 loci. We present clinical characterization of four index cases who have been diagnosed with ASD and who possess rare inherited or de novo microdeletions at 14q24.3-31.1, a region that overlaps exons of the alpha and/or beta isoforms of NRXN3. NRXN3 deletions were found in one father with subclinical autism and in a carrier mother and father without formal ASD diagnoses, indicating issues of penetrance and expressivity at this locus. Notwithstanding these clinical complexities, this report on ASD-affected individuals who harbor NRXN3 exonic deletions advances the understanding of the genetic etiology of autism, further enabling molecular diagnoses.
AB - The three members of the human neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3), encode neuronal adhesion proteins that have important roles in synapse development and function. In autism spectrum disorder (ASD), as well as in other neurodevelopmental conditions, rare exonic copy-number variants and/or point mutations have been identified in the NRXN1 and NRXN2 loci. We present clinical characterization of four index cases who have been diagnosed with ASD and who possess rare inherited or de novo microdeletions at 14q24.3-31.1, a region that overlaps exons of the alpha and/or beta isoforms of NRXN3. NRXN3 deletions were found in one father with subclinical autism and in a carrier mother and father without formal ASD diagnoses, indicating issues of penetrance and expressivity at this locus. Notwithstanding these clinical complexities, this report on ASD-affected individuals who harbor NRXN3 exonic deletions advances the understanding of the genetic etiology of autism, further enabling molecular diagnoses.
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U2 - 10.1016/j.ajhg.2011.11.025
DO - 10.1016/j.ajhg.2011.11.025
M3 - Article
C2 - 22209245
AN - SCOPUS:84855829221
SN - 0002-9297
VL - 90
SP - 133
EP - 141
JO - American journal of human genetics
JF - American journal of human genetics
IS - 1
ER -