Deletions of NRXN1 (Neurexin-1) Predispose to a Wide Spectrum of Developmental Disorders

被引：228

作者：

Ching, Michael S. L.

Shen, Yiping ^{[3
,7
]}

Tan, Wen-Hann ^{[4
]}

Jeste, Shafali S. ^{[5
]}

Morrow, Eric M. ^{[6
]}

Chen, Xiaoli ^{[7
,8
]}

Mukaddes, Nahit M. ^{[9
]}

Yoo, Seung-Yun ^{[4
]}

Hanson, Ellen

Hundley, Rachel

Austin, Christina ^{[4
]}

Becker, Ronald E.

Berry, Gerard T. ^{[4
]}

Driscoll, Katherine

Engle, Elizabeth C. ^{[5
,10
,11
,12
]}

Friedman, Sandra

Gusella, James F. ^{[2
,3
]}

Hisama, Fuki M. ^{[4
]}

Irons, Mira B. ^{[4
]}

Lafiosca, Tina

LeClair, Elaine

Miller, David T. ^{[4
,7
]}

Neessen, Michael

Picker, Jonathan D. ^{[4
]}

Rappaport, Leonard

Rooney, Cynthia M. ^{[5
]}

Sarco, Dean P. ^{[5
]}

Stoler, Joan M. ^{[4
]}

Walsh, Christopher A. ^{[4
,11
,13
]}

Wolff, Robert R. ^{[5
]}

Zhang, Ting ^{[8
]}

Nasir, Ramzi H. ^{[1
]}

Wu, Bai-Lin ^{[7
,14
,15
]}

机构：

[1] Harvard Univ, Sch Med, Div Dev Med, Childrens Hosp Boston, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Childrens Hosp Boston, Div Genet, Boston, MA USA

[5] Childrens Hosp Boston, Dept Neurol, Boston, MA USA

[6] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA

[7] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA

[8] Capital Inst Pediat, Dept Mol Immunol, Beijing, Peoples R China

[9] Istanbul Univ, Istanbul Fac Med, Dept Child Psychiat, Istanbul, Turkey

[10] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA

[11] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA

[12] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA USA

[13] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA

[14] Fudan Univ, Childrens Hosp, Shanghai 200433, Peoples R China

[15] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2010年 / 153B卷 / 04期

关键词：

NRXN1 (neurexin-1); developmental disorders; array CGH; NRXN1 exonic deletions; CNV; ALPHA-NEUREXINS; STRUCTURAL VARIANTS; NICOTINE DEPENDENCE; CA2+ CHANNELS; AUTISM; GENES; SCHIZOPHRENIA; ASSOCIATION; NEUROLIGINS; COMPLEX;

D O I：

10.1002/ajmg.b.31063

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P=8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders. (C) 2010 Wiley-Liss, Inc.

引用

页码：937 / 947

页数：11

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