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[P2.79]: Dynamic patterning of the vertebrate neural tube
Author(s) -
Ribeiro A.,
Briscoe J.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.209
Subject(s) - citation , computer science , library science , information retrieval , world wide web
Autism is a neurodevelopmental disorder of unclear etiology. Enlarged brain size is common in children with autism and recent studies suggest that an increased number of cortical excitatory neurons may underlie the large brain volume. Fibroblast Growth Factors (FGFs), a family of genes regulating cortical size and connectivity, may be involved in these developmental alterations. In this study we analyzed the involvement of FGF/FGFR signaling pathway genes in autism, through mutation screening and genetic association studies. Screening of mutations in exon 1 of the FGF2 gene was performed in 412 patients and 103 healthy controls. To further elucidate the involvement of the FGF genes in autism, we tested the FGF2, FGFR1, FGFR2 and FGFR3 genes for genetic association with autism in a sample of 238 nuclear families with one affected individual. For this purpose, 32 markers spanning the FGF2 gene, 44 SNPs in the FGFR1, 217 SNPs in FGFR2 gene and 35 SNPs in FGFR3 gene were analyzed using the Transmission Disequilibrium Test. We identified a novel p.T13 M mutation in exon 1 of FGF2 gene, in one male diagnosed with severe autism and macrocephaly. One marker in FGFR1 (p = 0.0312), four markers in introns 1, 2 and the 3’UTR region of the FGF2 gene (0.046 < p < 0.05) and one intergenic marker in downstream of the FGFR2 (p = 0.05) were nominally associated with autism. The genetic association analysis did not provide evidence for the FGF genes as common susceptibility factors for autism. However, the identified FGF2 mutation, together with a segmental duplication in the FGFR3 gene previously found in another autistic patient from our cohort, suggests that abnormal variation in these genes may represent a rare cause for autism. These findings further support the notion that rare sequence variation contributes to autism etiology.