Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder

被引：163

作者：

Vaags, Andrea K. ^{[1
]}

Lionel, Anath C. ^{[1
,2
]}

Sato, Daisuke ^{[1
]}

Goodenberger, McKinsey ^{[3
]}

Stein, Quinn P. ^{[4
]}

Curran, Sarah ^{[5
,6
]}

Ogilvie, Caroline ^{[7
,8
]}

Ahn, Joo Wook ^{[7
,8
]}

Drmic, Irene ^{[9
]}

Senman, Lili ^{[9
]}

Chrysler, Christina ^{[10
]}

Thompson, Ann ^{[10
]}

Russell, Carolyn ^{[10
]}

Prasad, Aparna ^{[1
]}

Walker, Susan ^{[1
]}

Pinto, Dalila ^{[1
]}

Marshall, Christian R. ^{[1
]}

Stavropoulos, Dimitri J. ^{[11
]}

Zwaigenbaum, Lonnie ^{[12
]}

Fernandez, Bridget A. ^{[13
,14
]}

Fombonne, Eric ^{[15
,16
]}

Bolton, Patrick F. ^{[5
,6
]}

Collier, David A. ^{[6
]}

Hodge, Jennelle C. ^{[3
]}

Roberts, Wendy ^{[9
,17
]}

Szatmari, Peter ^{[10
]}

Scherer, Stephen W. ^{[1
,2
]}

机构：

[1] Hosp Sick Children, Ctr Appl Genom, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada

[2] Univ Toronto, McLaughlin Ctr, Dept Mol Genet, Toronto, ON M5G 1L7, Canada

[3] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[4] Univ S Dakota, Sanford Sch Med, Sioux Falls, SD 57105 USA

[5] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England

[6] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Res Ctr, London SE5 8AF, England

[7] Guys Hosp, Cytogenet Lab, London SE1 9RT, England

[8] Kings Coll London, London SE1 9RT, England

[9] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada

[10] McMaster Univ, Offord Ctr Child Studies, Dept Psychiat & Behav Neurosci, Hamilton, ON L8S 4K1, Canada

[11] Hosp Sick Children, Dept Pediat Lab Med, Cytogenet Lab, Toronto, ON M5G 1L7, Canada

[12] Univ Alberta, Dept Pediat, Edmonton, AB T5G 0B7, Canada

[13] Mem Univ Newfoundland, Discipline Med, St John, NF A1B 3V6, Canada

[14] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada

[15] Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3Z 1P2, Canada

[16] McGill Univ, Montreal, PQ H3Z 1P2, Canada

[17] Univ Toronto, Bloorview Res Inst, Toronto, ON M4G 1R8, Canada

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 90卷 / 01期

基金：

加拿大创新基金会;

关键词：

COPY-NUMBER VARIATION; GENOME-WIDE ASSOCIATION; MENTAL-RETARDATION; STRUCTURAL VARIANTS; INCREASE RISK; DE-NOVO; SCHIZOPHRENIA; GENES; MUTATIONS; COMMON;

D O I：

10.1016/j.ajhg.2011.11.025

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：133 / 141

页数：9

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