Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders.

International audienceBACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD). Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD. METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA). RESULTS: We identified four patients with 15q11-q13 abnormalities: a supernumerary chromosome 15, a paternal interstitial duplication, and two subjects with Angelman syndrome, one with a maternal deletion and the other with a paternal uniparental disomy. CONCLUSIONS: Our results show that abnormalities of the 15q11-q13 region are a significant cause of ASD, accounting for approximately 1% of cases. Maternal interstitial 15q11-q13 duplications, previously reported to be present in 1% of patients with ASD, were not detected in our sample. Although paternal duplications of chromosome 15 remain phenotypically silent in the majority of patients, they can give rise to developmental delay and ASD in some subjects, suggesting that paternally expressed genes in this region can contribute to ASD, albeit with reduced penetrance compared with maternal duplications. These findings indicate that patients with ASD should be routinely screened for 15q genomic imbalances and methylation abnormalities and that MLPA is a reliable, rapid, and cost-effective method to perform this screening

Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome

Background: Genes involved in Tourette syndrome (TS) remain largely unknown. We aimed to identify genetic factors contributing to TS in a French cohort of 120 individuals using a combination of hypothesis-driven and exome-sequencing approaches. Methods: We first sequenced exons of SLITRK1-6 and HDC in the TS cohort and subsequently sequenced the exome of 12 individuals harboring rare variants in these genes to find additional rare variants contributing to the disorder under the hypothesis of oligogenic inheritance. We further screened three candidate genes (OPRK1, PCDH10, and NTSR2) preferentially expressed in the basal ganglia, and three additional genes involved in neurotensin and opioid signaling (OPRM1, NTS, and NTSR1), and compared variant frequencies in TS patients and 788 matched control individuals. We also investigated the impact of altering the expression of Oprk1 in zebrafish. Results: Thirteen ultrarare missense variants of SLITRK1-6 and HDC were identified in 12 patients. Exome sequencing in these patients revealed rare possibly deleterious variants in 3,041 genes, 54 of which were preferentially expressed in the basal ganglia. Comparison of variant frequencies altering selected candidate genes in TS and control individuals revealed an excess of potentially disrupting variants in OPRK1, encoding the opioid kappa receptor, in TS patients. Accordingly, we show that downregulation of the Oprk1 orthologue in zebrafish induces a hyperkinetic phenotype in early development. Discussion: These results support a heterogeneous and complex genetic etiology of TS, possibly involving rare variants altering the opioid pathway in some individuals, which could represent a novel therapeutic target in this disorder

Correction: Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome.

[This corrects the article DOI: 10.5334/tohm.464.]

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

24. E. R. Dodds, Willy Theiler, Pierre Hadot, Henri-Charles Puech, Heinrich Dörrie, Vincenzo Cilento, Richard Harder, H. R. Schwyzer, A. H. Armstrong, Paul Henry. Les Sources de Plotin, Dix exposés et discussions (Entretiens sur l'Antiquité classique, V). Fondation Hardt, Vandœuvres-Genève, 1960

Trouillard Jean. 24. E. R. Dodds, Willy Theiler, Pierre Hadot, Henri-Charles Puech, Heinrich Dörrie, Vincenzo Cilento, Richard Harder, H. R. Schwyzer, A. H. Armstrong, Paul Henry. Les Sources de Plotin, Dix exposés et discussions (Entretiens sur l'Antiquité classique, V). Fondation Hardt, Vandœuvres-Genève, 1960. In: Revue des Études Grecques, tome 74, fascicule 349-350, Janvier-juin 1961. pp. 328-329

A propos d'une étude sur Paul Valéry

Trouillard Jean. A propos d'une étude sur Paul Valéry. In: Bulletin de l'Association Guillaume Budé,n°2, juin 1952. pp. 57-61

111. Blumenthal (H. J.). Plotinus' Psychology. His doctrines of the Embodied Soul

Trouillard Jean. 111. Blumenthal (H. J.). Plotinus' Psychology. His doctrines of the Embodied Soul. In: Revue des Études Grecques, tome 88, fascicule 419-423, Janvier-décembre 1975. pp. 375-376

O. Neugebauer et II. B. Van Hoesen. Greek horoscopes

Trouillard Jean. O. Neugebauer et II. B. Van Hoesen. Greek horoscopes. In: Revue de l'histoire des religions, tome 158, n°2, 1960. p. 239

Christian Wolff, Cosmologia generalis edidit et curavit Joannes Ecole

Trouillard Jean. Christian Wolff, Cosmologia generalis edidit et curavit Joannes Ecole. In: Revue Philosophique de Louvain. Troisième série, tome 63, n°77, 1965. pp. 149-150