Semantic hyperpriming in schizophrenic patients: increased facilitation or impaired inhibition in semantic association processing?

International audiencePrevious studies analyzing semantic priming in schizophrenic patients have reported conflicting results. In the present study, we explored semantic priming in a sample of schizophrenic patients with mild thought disorders. We wondered if distinct cognitive processes, such as facilitation and/or inhibition, underlie semantic hyperpriming and are variously impaired in schizophrenic patients. Using a lexical decision task, we evaluated semantic priming in 15 schizophrenic patients (DSM-IV) with mild thought disorders and 15 healthy controls matched for sex, age, and education level. The task was designed to divide semantic priming into two additive components, namely facilitation effect and inhibition effect. One-sample t-tests were performed to investigate differences in semantic priming, facilitation, and inhibition within each group. ANOVAs were performed to compare the effects of semantic priming, facilitation, and inhibition between groups. Patients displayed greater semantic priming than controls (i.e., hyperpriming), but this was not due to increased facilitation in processing semantically related pairs. On the contrary, hyperpriming was the result of prolonged response time to process semantically unrelated pairs, corresponding to a requirement to inhibit unrelated information. We demonstrated semantic hyperpriming in stabilized schizophrenic patients with mild severity of symptoms. Thus, semantic hyperpriming may be an intrinsic feature of schizophrenia that is not related to the clinical state of patients. Semantic hyperpriming was due to an inhibition effect involved in processing semantically unrelated information not to increased facilitatory effect for related pairs

Eight previously unidentified mutations found in the OA1 ocular albinism gene

BACKGROUND: Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene. METHODS: The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments. RESULTS: We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found. CONCLUSION: The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand

Leber Congenital Amaurosis: Comprehensive Survey of the Genetic Heterogeneity, Refinement of the Clinical Definition, and Genotype-Phenotype Correlations as a Strategy for Molecular Diagnosis

Communicated by Jean-Claude Kaplan Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety. This wide genetic and physiologic heterogeneity that could largely increase in the coming years, hinders the molecular diagnosis in LCA patients. The genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here, we report a comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% patients. GUCY2D appeared to account for most LCA cases of our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%), and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited to search for phenotype variations. Sound genotype-phenotype correlations were found that allowed us to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rodcone dystrophy. Besides, objective ophthalmologic data allowed us to subdivide each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the heavy task of genotyping new patients but only if one has access to the most precise clinical history since birth

Etude des effets d'amorçage sémantique dans la schizophrénie

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Does hyperpriming reveal impaired spreading of activation in schizophrenia?

International audienceEnhancement of semantic priming effects (hyperpriming) has been well documented in schizophrenic patients (Minzenberg et al. 2002). In a previous study, we demonstrated that hyperpriming was related to a more pronounced requirement to inhibit unrelated information (Lecardeur et al. 2007). On the other hand, several authors have suggested that hyperpriming could reflect enhanced spreading of semantic activation in schizophrenia (Spitzer et al. 1993; Spitzer 1997; Moritz et al. 2001). So far, there are few reports that attempted to study the spreading of activation in schizophrenic patients compared to healthy controls, when the links between semantically related information were manipulated. Notably, authors stated that activation could consequently spread farther and further in the semantic networks of schizophrenic patients. Moreover, enhanced spreading of activation was hypothesized to be responsible of the appearance of thought and language disorders in schizophrenic patients. Consequently, we examined whether the manipulation of the type of connection and the semantic distance between prime and target can modulate semantic priming effects in schizophrenic patients compared to healthy controls

Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS) and report of temporal bone anomalies.

International audienceBranchio-oculo-facial syndrome (BOFS) is an autosomal-dominant condition characterized by three main features, respectively: branchial defects, ocular anomalies, and craniofacial defects including cleft lip and/or palate (CL/P). We report on one family with three affected, and two sporadic cases that have been found to carry missense mutations in the newly reported BOFS gene: TFAP2A. This report confirms the involvement of this transcription factor in this developmental syndrome with clinical variability. Moreover, we present CT scan temporal bone anomalies in the familial cases, related to branchial arch defects, highlighting the importance of radiological investigations for differential diagnosis

Genome sequencing for genetics diagnosis of patients with intellectual disability: the DEFIDIAG study

International audienceIntroduction: Intellectual Disability (ID) is the most common cause of referral to pediatric genetic centers, as it affects around 1-3% of the general population and is characterized by a wide genetic heterogeneity. The Genome Sequencing (GS) approach is expected to achieve a higher diagnostic yield than exome sequencing given its wider and more homogenous coverage, and, since theoretically, it can more accurately detect variations in regions traditionally not well captured and identify structural variants, or intergenic/deep intronic putatively pathological events. The decreasing cost of sequencing, the progress in data-management and bioinformatics, prompted us to assess GS efficiency as the first line procedure to identify the molecular diagnosis in patients without obvious ID etiology. This work is being carried out in the framework of the national French initiative for genomic medicine (Plan France Medecine Genomique 2025).Methods and Analysis: This multidisciplinary, prospective diagnostic study will compare the diagnostic yield of GS trio analysis (index case, father, mother) with the French core minimal reference strategy (Fragile-X testing, chromosomal microarray analysis and Gene Panel Strategy of 44 selected ID genes). Both strategies are applied in a blinded fashion, in parallel, in the same population of 1275 ID index cases with no obvious diagnosis (50% not previously investigated). Among them, a subgroup of 196 patients are randomized to undergo GS proband analysis in addition to GS trio analysis plus the French core minimal reference strategy, in order to compare their efficiency. The study also aims to identify the most appropriate strategy according to the clinical presentation of the patients, to evaluate the impact of deployment of GS on the families' diagnostic odyssey and the modification of their care, and to identify the advantages/difficulties for the patients and their families.Ethics Statement: The protocol was approved by the Ethics Committee Sud Mediterranee I and the French data privacy commission (CNIL, authorization 919361