PMID- 19002214
OWN - NLM
STAT- MEDLINE
DCOM- 20090901
LR  - 20220309
IS  - 1476-5438 (Electronic)
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 17
IP  - 6
DP  - 2009 Jun
TI  - MET and autism susceptibility: family and case-control studies.
PG  - 749-58
LID - 10.1038/ejhg.2008.215 [doi]
AB  - Autism is a common, severe and highly heritable neurodevelopmental disorder. The 
      International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen 
      for linkage in affected sib-pair families identified a chromosome 7q 
      susceptibility locus (AUTS1), that has subsequently shown evidence of increased 
      sharing in several independent multiplex samples and in two meta-analyses. Taking 
      into account the location of the MET gene under this linkage peak, and the fact 
      that it has recently been reported to be associated with autism, the gene was 
      further analyzed as a promising autism candidate. The gene encodes a 
      transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter 
      factor (HGF/SF). MET is best known as an oncogene, but its signalling also 
      participates in immune function, peripheral organ development and repair, and the 
      development of the cerebral cortex and cerebellum (all of which have been 
      observed earlier as being disregulated in individuals with autism). Here we 
      present a family-based association analysis covering the entire MET locus. 
      Significant results were obtained in both single locus and haplotype approaches 
      with a single nucleotide polymorphism in intron 1 (rs38845, P<0.004) and with one 
      intronic haplotype (AAGTG, P<0.009) in 325 multiplex IMGSAC families and 10 
      IMGSAC trios. Although these results failed to replicate in an independent sample 
      of 82 Italian trios, the association itself was confirmed by a case-control 
      analysis performed using the Italian cohort (P<0.02). The previously reported 
      positive association of rs1858830 failed to replicate in this study. Overall, our 
      findings provide further evidence that MET may play a role in autism 
      susceptibility.
FAU - Sousa, Ines
AU  - Sousa I
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Clark, Taane G
AU  - Clark TG
FAU - Toma, Claudio
AU  - Toma C
FAU - Kobayashi, Kazuhiro
AU  - Kobayashi K
FAU - Choma, Maja
AU  - Choma M
FAU - Holt, Richard
AU  - Holt R
FAU - Sykes, Nuala H
AU  - Sykes NH
FAU - Lamb, Janine A
AU  - Lamb JA
FAU - Bailey, Anthony J
AU  - Bailey AJ
FAU - Battaglia, Agatino
AU  - Battaglia A
FAU - Maestrini, Elena
AU  - Maestrini E
FAU - Monaco, Anthony P
AU  - Monaco AP
CN  - International Molecular Genetic Study of Autism Consortium (IMGSAC)
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 075491/WT_/Wellcome Trust/United Kingdom
GR  - G0601030/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081112
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
CIN - Eur J Hum Genet. 2009 Jun;17(6):699-700. PMID: 19002212
MH  - Autistic Disorder/*genetics
MH  - Case-Control Studies
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Growth Factor/*genetics
PMC - PMC2685893
MID - UKMS2583
OID - NLM: UKMS2583
EDAT- 2008/11/13 09:00
MHDA- 2009/09/02 06:00
PMCR- 2009/06/01
CRDT- 2008/11/13 09:00
PHST- 2008/11/13 09:00 [pubmed]
PHST- 2009/09/02 06:00 [medline]
PHST- 2008/11/13 09:00 [entrez]
PHST- 2009/06/01 00:00 [pmc-release]
AID - ejhg2008215 [pii]
AID - 10.1038/ejhg.2008.215 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2009 Jun;17(6):749-58. doi: 10.1038/ejhg.2008.215. Epub 2008 Nov 
      12.