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Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders

Laroche, Fabricea; Ramoz, Nicolasb; Leroy, Sophiec; Fortin, Céliad; Rousselot-Paillet, Bérangèred f; Philippe, Anneg; Colleaux, Laurenceg; Bresson, Jean-Louise; Mogenet, Agnèse; Golse, Bernardd f; Mouren-Simeoni, Marie-Christineb h; Gorwood, Philipb; Galli, Thierrya; Simonneau, Michelb; Krebs, Marie-Odilec; Robel, Laurenced f

doi: 10.1097/YPG.0b013e3283060fa5
Original Articles

Objectives Autism (MIM♯209850) and schizophrenia (MIM♯181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2, ARX, and FOXP2 genes whereas only three studies of EN2, OTX2, and FOXP2 were performed on schizophrenia. Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats in schizophrenia, autism, and idiopathic mental retardation.

Methods We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering from schizophrenia (247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls).

Results Novel deletions and insertions of coding trinucleotide repeats were found in the DLX2, HOXA1, and FOXP2 genes. Most of these variations were detected in controls and no difference in their distribution was observed between patient and control groups. Two different polymorphisms in FOXP2 were, however, found only in autistic patients and the functional consequences of these variations of repeats have to be characterized and correlated to particular clinical features.

Conclusion This study did not identify specific disease risk variants of trinucleotide repeats in OTX1, EN1, DLX2, HOXA1, and FOXP2 candidate genes in neurodevelopmental psychiatric disorders.

aINSERM AVENIR, Institut Jacques Monod UMR7592

bINSERM U675, IFR02, Faculté de médecine X Bichat, Université Paris 7

cINSERM U796, Centre hospitalier Sainte-Anne, Université Paris 5

dService de Psychiatrie de l'Enfant et de l'Adolescent



gINSERM U781, Hôpital Necker-Enfants Malades

hAP-HP, Hôpital Robert Debré, Service de Psychopathologie de l'Enfant et de l'Adolescent, Paris, France

Correspondence to Dr Laurence Robel, Service de Psychiatrie de l'Enfant et de l'Adolescent, Hôpital Necker-Enfants Malades, 149 Avenue de Sèvres, Paris 75015, France

Tel: +33 1 44 49 45 61; fax: +33 1 44 49 47 10;


Received 5 November 2007 Revised 3 March 2008 Accepted 29 March 2008

© 2008 Lippincott Williams & Wilkins, Inc.