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Xq27 FRAXA Locus is a Strong Candidate for Dyslexia: Evidence from a Genome-Wide Scan in French Families

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Abstract

Dyslexia is a frequent neurodevelopmental learning disorder. To date, nine susceptibility loci have been identified, one of them being DYX9, located in Xq27. We performed the first French SNP linkage study followed by candidate gene investigation in dyslexia by studying 12 multiplex families (58 subjects) with at least two children affected, according to categorical restrictive criteria for phenotype definition. Significant results emerged on Xq27.3 within DYX9. The maximum multipoint LOD score reached 3,884 between rs12558359 and rs454992. Within this region, seven candidate genes were investigated for mutations in exonic sequences (CXORF1, CXORF51, SLITRK2, FMR1, FMR2, ASFMR1, FMR1NB), all having a role during brain development. We further looked for 5′UTR trinucleotide repeats in FMR1 and FMR2 genes. No mutation or polymorphism co-segregating with dyslexia was found. This finding in French families with Dyslexia showed significant linkage on Xq27.3 enclosing FRAXA, and consequently confirmed the DYX9 region as a robust susceptibility locus. We reduced the previously described interval from 6.8 (DXS1227–DXS8091) to 4 Mb also disclosing a higher LOD score.

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Acknowledgments

This work was supported by a grant of the French Ministry of Education and Research. We thank D Raine, AS Galloux, AG Piller, G Turlotte, E Schweitzer, S Heath, and C Blanc-Tailleur for their valuable contribution. We are also very grateful to the families for their participation to the study.

Conflict of interest

All authors report no biomedical financial disclosures or potential conflicts of interest.

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Authors and Affiliations

  1. UMR INSERM U930, François Rabelais University, Tours, France

    M. Huc-Chabrolle, P. Vourc’h, R. A. Thepault, A. Toutain, M. Raynaud, C. Andres, F. Laumonnier & F. Bonnet-Brilhault

  2. Department of Child Psychiatry, University Hospitals of Tours, Tours, France

    M. Huc-Chabrolle, G. Tripi & F. Bonnet-Brilhault

  3. CEA/Centre National de Génotypage, Évry, France

    C. Charon & J. Hager

  4. INSERM U 1079, Rouen, France

    A. Guilmatre, S. Le Gallic & D. Campion

  5. Department of Molecular Biochemistry, University Hospitals of Tours, Tours, France

    P. Vourc’h, R. A. Thepault & C. Andres

  6. University of Palermo, Palermo, Italy

    G. Tripi

  7. Reference Centre for Learning Disability, University Hospitals of Tours, Tours, France

    M. Huc-Chabrolle, M. A. Barthez, E. Sizaret & F. Bonnet-Brilhault

  8. Department of Human Genetics, University Hospitals of Tours, Tours, France

    A. Toutain, M. Raynaud & F. Laumonnier

  9. Centre Universitaire de Pédopsychiatrie, CHRU de Tours, Hôpital Bretonneau, 2, Bd Tonnellé, 37044, Tours Cedex 9, France

    M. Huc-Chabrolle

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  1. M. Huc-Chabrolle
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  2. C. Charon
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  3. A. Guilmatre
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Correspondence to M. Huc-Chabrolle.

Additional information

Edited by Stacey Cherny.

M. Huc-Chabrolle and C. Charon contributed equally to this study.

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Huc-Chabrolle, M., Charon, C., Guilmatre, A. et al. Xq27 FRAXA Locus is a Strong Candidate for Dyslexia: Evidence from a Genome-Wide Scan in French Families. Behav Genet 43, 132–140 (2013). https://doi.org/10.1007/s10519-012-9575-5

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