Association of common variants in the Joubert syndrome gene (AHI1) with autism

Center for Autism Research and Treatment Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Human Molecular Genetics (Impact Factor: 6.39). 10/2008; 17(24):3887-96. DOI: 10.1093/hmg/ddn291
Source: PubMed


It has been suggested that autism, like other complex genetic disorders, may benefit from the study of rare or Mendelian variants
associated with syndromic or non-syndromic forms of the disease. However, there are few examples in which common variation
in genes causing a Mendelian neuropsychiatric disorder has been shown to contribute to disease susceptibility in an allied
common condition. Joubert syndrome (JS) is a rare recessively inherited disorder, with mutations reported at several loci
including the gene Abelson’s Helper Integration 1 (AHI1). A significant proportion of patients with JS, in some studies up to 40%, have been diagnosed with autism spectrum disorder
(ASD) and several linkage studies in ASD have nominally implicated the region on 6q where AHI1 resides. To evaluate AHI1 in ASD, we performed a three-stage analysis of AHI1 as an a priori candidate gene for autism. Re-sequencing was first used to screen AHI1, followed by two subsequent association studies, one limited and one covering the gene more completely, in Autism Genetic
Resource Exchange (AGRE) families. In stage 3, we found evidence of an associated haplotype in AHI1 with ASD after correction for multiple comparisons, in a region of the gene that had been previously associated with schizophrenia.
These data suggest a role for AHI1 in common disorders affecting human cognition and behavior.

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Available from: Joseph Gleeson, Dec 17, 2013
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    • "Joubert syndrome is characterized by ataxia, abnormal breathing patterns, sleep apnea, abnormal eye and tongue movements and hypotonia, as well as distinct malformations of cerebellum and brain stem. A high percentage of patients with Joubert syndrome have been diagnosed with autism spectrum disorder [95]. One of the first genes identified to be involved in the pathogenesis of this syndrome was ‘Abelson’s Helper Integration 1’ (AHI1) [96]. "
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    • "It is worth noting that several features of autism spectrum disorder (ASD), such as deficits in social behaviour, language dysfunction and repetitive behaviours, have also been described in up to 40% of patients with JS [130, 131]. A three-stage family-based association study has demonstrated evidence of an associated haplotype in AHI-1 with ASD in a region of the genes that has also been associated with schizophrenia [25]. These findings suggest an important role for AHI1 in common brain disorders affecting human cognition and behaviour. "
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