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Thursday, May 15, 2008
Champagne Terrace/Bordeaux (Novotel London West)
11:30 AM
Background:
Positional cloning of chromosomal translocation breakpoints in autism patients is a valuable strategy towards the identification of candidate genes, especially in isolated autism, and when the aberration is de novo and family history is negative for autism. (1)
Objectives:
We describe a nondysmorphic patient with autism and full scale IQ of 76, who carries a complex translocation involving chromosomes 3,5,16 and a pericentromeric inversion on chromosome 4.
Methods:
1Mb BAC array-CHG was performed to uncover possible submicroscopic imbalances. The breakpoints were finemapped with FISH.
Results:
On array-CGH, a ~1Mb microdeletion encompassing the clone NONSC8G10 was detected. Only 1 gene, cadherin-11 (CDH11) was located in this region. Of the remaining 6 breakpoints, one disrupted the AK13094 gene, another was near GFOD and RANBP10.
Conclusions:
In this patient with a complex chromosomal aberration, the CDH11 gene was found to be deleted on one allele. Cdh11 is expressed in the lymbic system and hippocampus in mice and may play a role in the organisation of central synapses.(2) Interestingly, there is evidence that altered synaptogenesis is implicated in the pathogenesis of autism. For instance, the post-synaptic cell adhesion molecules NLGN-3 and -4 are implicated in autism through their role in the establishment of fully functional presynaptic terminals in contacting axons.(3) Thus, CHD11 represents both a positional and functional candidate gene for autism. Mutation screening in a larger cohort of autism patients is ongoing.
(1)Castermans D et al (2003) The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism. J Med Genet 40(5) 352-6
(2)Manabe T et al (2000) Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses. J Mol Neurosci 15(6) 534-46
(3) Persico AM, Bourgeron T (2006) Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 29(7) 349-58
Positional cloning of chromosomal translocation breakpoints in autism patients is a valuable strategy towards the identification of candidate genes, especially in isolated autism, and when the aberration is de novo and family history is negative for autism. (1)
Objectives:
We describe a nondysmorphic patient with autism and full scale IQ of 76, who carries a complex translocation involving chromosomes 3,5,16 and a pericentromeric inversion on chromosome 4.
Methods:
1Mb BAC array-CHG was performed to uncover possible submicroscopic imbalances. The breakpoints were finemapped with FISH.
Results:
On array-CGH, a ~1Mb microdeletion encompassing the clone NONSC8G10 was detected. Only 1 gene, cadherin-11 (CDH11) was located in this region. Of the remaining 6 breakpoints, one disrupted the AK13094 gene, another was near GFOD and RANBP10.
Conclusions:
In this patient with a complex chromosomal aberration, the CDH11 gene was found to be deleted on one allele. Cdh11 is expressed in the lymbic system and hippocampus in mice and may play a role in the organisation of central synapses.(2) Interestingly, there is evidence that altered synaptogenesis is implicated in the pathogenesis of autism. For instance, the post-synaptic cell adhesion molecules NLGN-3 and -4 are implicated in autism through their role in the establishment of fully functional presynaptic terminals in contacting axons.(3) Thus, CHD11 represents both a positional and functional candidate gene for autism. Mutation screening in a larger cohort of autism patients is ongoing.
(1)Castermans D et al (2003) The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism. J Med Genet 40(5) 352-6
(2)Manabe T et al (2000) Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses. J Mol Neurosci 15(6) 534-46
(3) Persico AM, Bourgeron T (2006) Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 29(7) 349-58