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Master Thesis

Aspects cliniques et génétiques des Troubles du Spectre Autistique : familles multiplexes et anomalies des Neuroligines

Abstract : Autism Spectrum Disorder is a neurodeveloppemental disease with an estimated prevalence of 1% and an unequal sexratio (1 girl for 4 boys in typical autism). Patients exhibit social communication difficulties, restrictive interests, stereotyped behaviors and sometimes langage delay. ASD is known as the most heritable psychiatric disease (56 to 95%), in favor of genetic aetiologies. Family studies where several individuals have ASD (multiplex families(MPX)) aim to establish genotype-phenotype correlation in a cohort. A study including 49 ASD patients and 88 related (from 17 MPX families included in PA- RIS international cohort [Paris Autism Research International Sibpairs]) shows an important overexpression of psychiatric comorbidities in ASD patients and in related people compared to prevalence in the general population (73.7%, 70% and 18.6% respectively) (p-value=2.3e- 13). A similar rate of de novo exonic events in ASD patients and in siblings is found (1.68 vs 1.07 respectively). “Multiple hit model” describes phenotypic translation of additive de novo and inherited deleterious variants within a same individual. A meta-analysis of the neuroligin genes family (NLGN1, NLGN2, NLGN3, NLGN4X, NLGN4Y) in ASD is used to compare the phenotype-genotype link and to compare these results with patients with NLGN4Y deletions and duplications in a cohort of 212 ASD boys. Deeper knowledge in pathophysiological mecha- nisms using multiplex family studies will allow in the future to find new cand! idate genes, to develop pharmacogenetic approaches specific of a ASD patient genetic abnormalities.
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Master Thesis
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Contributor : Bu Carreire Université de Bordeaux <>
Submitted on : Monday, October 19, 2015 - 3:51:29 PM
Last modification on : Friday, August 25, 2017 - 1:08:15 AM
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  • HAL Id : dumas-01217434, version 1



Marie Ducloy. Aspects cliniques et génétiques des Troubles du Spectre Autistique : familles multiplexes et anomalies des Neuroligines. Médecine humaine et pathologie. 2015. ⟨dumas-01217434⟩



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