Heterozygous FA2H mutations in autism spectrum disorders. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles BMC Medical Genetics Year : 2013

Heterozygous FA2H mutations in autism spectrum disorders.

Claire Leblond
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  • PersonId : 949745
Henrik Anckarsäter
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  • PersonId : 920012
Maria Rastam
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  • PersonId : 949747
Mary Coleman
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  • PersonId : 949751
Hiroko Hama
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  • PersonId : 949752
Edwin Cook
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  • PersonId : 949753


BACKGROUND: Widespread abnormalities in white matter development are frequently reported in cases of autism spectrum disorders (ASD) and could be involved in the disconnectivity suggested in these disorders. Homozygous mutations in the gene coding for fatty-acid 2-hydroxylase (FA2H), an enzyme involved in myelin synthesis, are associated with complex leukodystrophies, but little is known about the functional impact of heterozygous FA2H mutations. We hypothesized that rare deleterious heterozygous mutations of FA2H might constitute risk factors for ASD. METHODS: We searched deleterious mutations affecting FA2H, by genotyping 1256 independent patients with ASD genotyped using Genome Wide SNP arrays, and also by sequencing in independent set of 186 subjects with ASD and 353 controls. We then explored the impact of the identified mutations by measuring FA2H enzymatic activity and expression, in transfected COS7 cells. RESULTS: One heterozygous deletion within 16q22.3-q23.1 including FA2H was observed in two siblings who share symptoms of autism and severe cognitive impairment, axial T2-FLAIR weighted MRI posterior periventricular white matter lesions. Also, two rare non-synonymous mutations (R113W and R113Q) were reported. Although predictive models suggested that R113W should be a deleterious, we did not find that FA2H activity was affected by expression of the R113W mutation in cultured COS cells. CONCLUSIONS: While our results do not support a major role for FA2H coding variants in ASD, a screening of other genes related to myelin synthesis would allow us to better understand the role of non-neuronal elements in ASD susceptibility.


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Dates and versions

inserm-00918083 , version 1 (12-12-2013)



Isabelle Scheid, Anna Maruani, Guillaume Huguet, Claire Leblond, Gudrun Nygren, et al.. Heterozygous FA2H mutations in autism spectrum disorders.. BMC Medical Genetics, 2013, 14 (1), pp.124. ⟨10.1186/1471-2350-14-124⟩. ⟨inserm-00918083⟩
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