Rare deletions at the neurexin 3 locus in autism spectrum disorder.
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.
Program in Genetics and Genome Biology, The Centre for Applied Genomics, the Hospital for Sick Children, Toronto, Ontario, Canada.
Andrea K
AK
Vaags
Anath C
AC
Lionel
Daisuke
D
Sato
McKinsey
M
Goodenberger
Quinn P
QP
Stein
Sarah
S
Curran
Caroline
C
Ogilvie
Joo Wook
JW
Ahn
Irene
I
Drmic
Lili
L
Senman
Christina
C
Chrysler
Ann
A
Thompson
Carolyn
C
Russell
Aparna
A
Prasad
Susan
S
Walker
Dalila
D
Pinto
Christian R
CR
Marshall
Dimitri J
DJ
Stavropoulos
Lonnie
L
Zwaigenbaum
Bridget A
BA
Fernandez
Eric
E
Fombonne
Patrick F
PF
Bolton
David A
DA
Collier
Jennelle C
JC
Hodge
Wendy
W
Roberts
Peter
P
Szatmari
Stephen W
SW
Scherer
D000293:Adolescent; D000328:Adult; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D056426:Genetic Loci; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D055815:Young Adult
D009419:Nerve Tissue Proteins; C082354:neurexin IIIalpha