Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.
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.
Ching
Michael S L
MS
Division of Developmental Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Shen
Yiping
Y
Tan
Wen-Hann
WH
Jeste
Shafali S
SS
Morrow
Eric M
EM
Chen
Xiaoli
X
Mukaddes
Nahit M
NM
Yoo
Seung-Yun
SY
Hanson
Ellen
E
Hundley
Rachel
R
Austin
Christina
C
Becker
Ronald E
RE
Berry
Gerard T
GT
Driscoll
Katherine
K
Engle
Elizabeth C
EC
Friedman
Sandra
S
Gusella
James F
JF
Hisama
Fuki M
FM
Irons
Mira B
MB
Lafiosca
Tina
T
LeClair
Elaine
E
Miller
David T
DT
Neessen
Michael
M
Picker
Jonathan D
JD
Rappaport
Leonard
L
Rooney
Cynthia M
CM
Sarco
Dean P
DP
Stoler
Joan M
JM
Walsh
Christopher A
CA
Wolff
Robert R
RR
Zhang
Ting
T
Nasir
Ramzi H
RH
Wu
Bai-Lin
BL
D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007805:Language Development Disorders / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics; D017384:Sequence Deletion
Neurosci Lett. 2006 Nov 27;409(1):10-3
17034946
Trends Genet. 1998 Jan;14(1):20-6
9448462
Int J Dev Biol. 2006;50(1):39-46
16323076
Genome Res. 2002 Jun;12(6):996-1006
12045153
PLoS Genet. 2009 Feb;5(2):e1000373
19197363
J Neurosci. 2006 Oct 11;26(41):10599-613
17035546
Hum Mol Genet. 2008 Feb 1;17(3):458-65
17989066
Nature. 2008 Sep 11;455(7210):237-41
18668038
Am J Hum Genet. 2008 Jan;82(1):165-73
18179895
Am J Hum Genet. 2004 Mar;74(3):552-7
14963808
Nature. 2009 May 28;459(7246):569-73
19404257
Neuron. 1995 Mar;14(3):497-507
7695896
J Cell Biol. 2001 Jul 23;154(2):435-45
11470830
Am J Hum Genet. 2007 Dec;81(6):1289-97
17999366
Am J Hum Genet. 2008 Jan;82(1):160-4
18179894
Lancet Neurol. 2004 Oct;3(10):577
15380151
J Biol Chem. 1996 Feb 2;271(5):2676-82
8576240
Biol Psychiatry. 2004 Feb 1;55(3):323-6
14744477
Science. 2008 Apr 25;320(5875):539-43
18369103
Cell. 2004 Dec 29;119(7):1013-26
15620359
Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6137-42
15837930
Mol Psychiatry. 2002;7(3):302-10
11920157
Am J Hum Genet. 2008 Feb;82(2):477-88
18252227
Brain. 2004 Aug;127(Pt 8):1811-21
15215213
Nat Struct Mol Biol. 2008 Jan;15(1):50-6
18084303
J Neurosci. 1995 Apr;15(4):2849-56
7722633
Am J Hum Genet. 2009 Feb;84(2):148-61
19166990
Hum Mol Genet. 2008 Jun 1;17(11):1569-77
18270208
Genomics. 2002 Jun;79(6):849-59
12036300
J Neurosci. 2005 Apr 27;25(17):4330-42
15858059
Neurosci Lett. 2008 Jun 27;438(3):368-70
18490107
Hum Mol Genet. 2007 Jan 1;16(1):24-35
17158188
Am J Hum Genet. 2008 Jan;82(1):199-207
18179900
Nature. 2003 Jun 26;423(6943):939-48
12827191
Eur J Hum Genet. 2008 May;16(5):614-8
18231125
Hum Mol Genet. 2009 Mar 1;18(5):988-96
18945720
Nature. 2009 May 28;459(7246):528-33
19404256
Cell. 1995 May 5;81(3):435-43
7736595
Nature. 2008 Oct 16;455(7215):903-11
18923512
Structure. 2007 Jun;15(6):693-705
17562316
Science. 2008 Jul 11;321(5886):218-23
18621663
Neuron. 2007 Dec 20;56(6):992-1003
18093522
Am J Hum Genet. 2008 Jan;82(1):150-9
18179893
Science. 1992 Jul 3;257(5066):50-6
1621094
Am J Hum Genet. 2008 Oct;83(4):504-10
18940311
Nat Genet. 2007 Mar;39(3):319-28
17322880
J Comp Neurol. 2007 May 10;502(2):261-74
17347997
Curr Opin Neurobiol. 2007 Feb;17(1):103-11
17275283
Nat Genet. 2007 Jan;39(1):25-7
17173049
J Med Genet. 2008 Apr;45(4):239-43
18057082
DNA Res. 1998 Feb 28;5(1):31-9
9628581