Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder

Andrea K. Vaags; Anath C. Lionel; Daisuke Sato; McKinsey Goodenberger; Quinn P. Stein; Sarah Curran; Caroline Ogilvie; Joo Wook Ahn; Irene Drmic; Lili Senman; Christina Chrysler; Ann Thompson; Carolyn Russell; Aparna Prasad; Susan Walker; Dalila Pinto; Christian R. Marshall; Dimitri J. Stavropoulos; Lonnie Zwaigenbaum; Bridget A. Fernandez; Eric Fombonne; Patrick F. Bolton; David A. Collier; Jennelle C. Hodge; Wendy Roberts; Peter Szatmari; Stephen W. Scherer

doi:10.1016/j.ajhg.2011.11.025

Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder

Andrea K. Vaags, Anath C. Lionel, Daisuke Sato, McKinsey Goodenberger, Quinn P. Stein, Sarah Curran, Caroline Ogilvie, Joo Wook Ahn, Irene Drmic, Lili Senman, Christina Chrysler, Ann Thompson, Carolyn Russell, Aparna Prasad, Susan Walker, Dalila Pinto, Christian R. Marshall, Dimitri J. Stavropoulos, Lonnie Zwaigenbaum, Bridget A. FernandezEric Fombonne, Patrick F. Bolton, David A. Collier, Jennelle C. Hodge, Wendy Roberts, Peter Szatmari, Stephen W. Scherer

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Abstract

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.

Original language	English
Pages (from-to)	133 - 141
Number of pages	9
Journal	American Journal of Human Genetics
Volume	90
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2011.11.025
Publication status	Published - 13 Jan 2012

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Vaags, A. K., Lionel, A. C., Sato, D., Goodenberger, M., Stein, Q. P., Curran, S., Ogilvie, C., Ahn, J. W., Drmic, I., Senman, L., Chrysler, C., Thompson, A., Russell, C., Prasad, A., Walker, S., Pinto, D., Marshall, C. R., Stavropoulos, D. J., Zwaigenbaum, L., ... Scherer, S. W. (2012). Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder. American Journal of Human Genetics, 90(1), 133 - 141. https://doi.org/10.1016/j.ajhg.2011.11.025

@article{c54d3456536e4ffbb6fa5c5abbe77141,

title = "Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder",

abstract = "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.",

author = "Vaags, {Andrea K.} and Lionel, {Anath C.} and Daisuke Sato and McKinsey Goodenberger and Stein, {Quinn P.} and Sarah Curran and Caroline Ogilvie and Ahn, {Joo Wook} and Irene Drmic and Lili Senman and Christina Chrysler and Ann Thompson and Carolyn Russell and Aparna Prasad and Susan Walker and Dalila Pinto and Marshall, {Christian R.} and Stavropoulos, {Dimitri J.} and Lonnie Zwaigenbaum and Fernandez, {Bridget A.} and Eric Fombonne and Bolton, {Patrick F.} and Collier, {David A.} and Hodge, {Jennelle C.} and Wendy Roberts and Peter Szatmari and Scherer, {Stephen W.}",

year = "2012",

month = jan,

day = "13",

doi = "10.1016/j.ajhg.2011.11.025",

language = "English",

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journal = "American Journal of Human Genetics",

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Vaags, AK, Lionel, AC, Sato, D, Goodenberger, M, Stein, QP, Curran, S, Ogilvie, C, Ahn, JW, Drmic, I, Senman, L, Chrysler, C, Thompson, A, Russell, C, Prasad, A, Walker, S, Pinto, D, Marshall, CR, Stavropoulos, DJ, Zwaigenbaum, L, Fernandez, BA, Fombonne, E, Bolton, PF , Collier, DA, Hodge, JC, Roberts, W, Szatmari, P & Scherer, SW 2012, 'Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder', American Journal of Human Genetics, vol. 90, no. 1, pp. 133 - 141. https://doi.org/10.1016/j.ajhg.2011.11.025

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.

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.

U2 - 10.1016/j.ajhg.2011.11.025

DO - 10.1016/j.ajhg.2011.11.025

M3 - Article

SN - 1537-6605

VL - 90

SP - 133

EP - 141

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder

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