PMID- 19546099
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20211020
IS  - 1468-6244 (Electronic)
IS  - 0022-2593 (Print)
IS  - 0022-2593 (Linking)
VI  - 47
IP  - 2
DP  - 2010 Feb
TI  - A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a 
      novel candidate for autism.
PG  - 81-90
LID - 10.1136/jmg.2008.065821 [doi]
AB  - BACKGROUND: A child with autism and mild microcephaly was found to have a de novo 
      3.3 Mb microdeletion on chromosome 1p34.2p34.3. The hypothesis is tested that 
      this microdeletion contains one or more genes that underlie the autism phenotype 
      in this child and in other children with autism spectrum disorders. METHODS: To 
      search for submicroscopic chromosomal rearrangements in the child, array 
      comparative genomic hybridisation (aCGH) was performed using a 19 K whole genome 
      human bacterial artificial chromosome (BAC) array and the Illumina 610-Quad 
      BeadChip microarray. Ingenuity pathway analysis (IPA) was used to construct 
      functional biological networks to identify candidate autism genes. To identify 
      putative functional variants in candidate genes, mutation screening was performed 
      using polymerase chain reaction (PCR) based Sanger sequencing in 512 unrelated 
      autism patients and 462 control subjects. RESULTS: A de novo 3.3 Mb deletion 
      containing approximately 43 genes in chromosome 1p34.2p34.3 was identified and 
      subsequently confirmed using fluorescence in situ hybridization (FISH). 
      Literature review and bioinformatics analyses identified Regulating Synaptic 
      Membrane Exocytosis 3 (RIMS3) as the most promising autism candidate gene. 
      Mutation screening of this gene in autism patients identified five inherited 
      coding variants, including one (p.E177A) that segregated with the autism 
      phenotype in a sibship, was predicted to be deleterious, and was absent in 1161 
      controls. CONCLUSIONS: This case report and mutation screening data suggest that 
      RIMS3 is an autism causative or contributory gene. Functional studies of RIMS3 
      variants such as p.E177A should provide additional insight into the role of 
      synaptic proteins in the pathophysiology of autism.
FAU - Kumar, Ravinesh A
AU  - Kumar RA
AD  - Department of Human Genetics, University of Chicago,Chicago, Illinois 60637, USA.
FAU - Sudi, Jyotsna
AU  - Sudi J
FAU - Babatz, Timothy D
AU  - Babatz TD
FAU - Brune, Camille W
AU  - Brune CW
FAU - Oswald, Donald
AU  - Oswald D
FAU - Yen, Mayon
AU  - Yen M
FAU - Nowak, Norma J
AU  - Nowak NJ
FAU - Cook, Edwin H
AU  - Cook EH
FAU - Christian, Susan L
AU  - Christian SL
FAU - Dobyns, William B
AU  - Dobyns WB
LA  - eng
GR  - U24 MH081810/MH/NIMH NIH HHS/United States
GR  - 1U24MH081810/MH/NIMH NIH HHS/United States
GR  - R01 NS050375/NS/NINDS NIH HHS/United States
GR  - R01 NS051812/NS/NINDS NIH HHS/United States
GR  - AS1583/AS/Autism Speaks/United States
GR  - R01-NS051812/NS/NINDS NIH HHS/United States
GR  - P30 CA01605632/CA/NCI NIH HHS/United States
GR  - R01-NS050375/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090621
PL  - England
TA  - J Med Genet
JT  - Journal of medical genetics
JID - 2985087R
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RIMS3 protein, human)
SB  - IM
MH  - Amino Acid Substitution
MH  - Autistic Disorder/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Comparative Genomic Hybridization
MH  - DNA Mutational Analysis
MH  - Databases, Genetic
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Membrane Transport Proteins/*genetics
MH  - Mutation, Missense
MH  - Nerve Tissue Proteins/*genetics
MH  - *Sequence Deletion
PMC - PMC2921284
COIS- Competing interests: None.
EDAT- 2009/06/24 09:00
MHDA- 2010/05/07 06:00
PMCR- 2009/06/21
CRDT- 2009/06/24 09:00
PHST- 2009/06/24 09:00 [entrez]
PHST- 2009/06/24 09:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
PHST- 2009/06/21 00:00 [pmc-release]
AID - jmg.2008.065821 [pii]
AID - jmg065821 [pii]
AID - 10.1136/jmg.2008.065821 [doi]
PST - ppublish
SO  - J Med Genet. 2010 Feb;47(2):81-90. doi: 10.1136/jmg.2008.065821. Epub 2009 Jun 
      21.