دورية أكاديمية
Heterozygous deletion of the LRFN2 gene is associated with working memory deficits
| العنوان: | Heterozygous deletion of the LRFN2 gene is associated with working memory deficits |
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| المؤلفون: | Thevenon, Julien, Souchay, Céline, Seabold, Gail K, Dygai-Cochet, Inna, Callier, Patrick, Gay, Sébastien, Corbin, Lucie, Duplomb, Laurence, Thauvin-Robinet, Christel, Masurel-Paulet, Alice, El Chehadeh, Salima, Avila, Magali, Minot, Delphine, Guedj, Eric, Chancenotte, Sophie, Bonnet, Marlène, Lehalle, Daphne, Wang, Ya-Xian, Kuentz, Paul, Huet, Frédéric, Mosca-Boidron, Anne-Laure, Marle, Nathalie, Petralia, Ronald S, Faivre, Laurence |
| المساهمون: | Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire d'Etude de l'Apprentissage et du Développement Dijon (LEAD), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Neurochem lab (NIDCD), Nationale Institute of Health, Service de Médecine Nucléaire, Centre Régional de Lutte contre le cancer Georges-François Leclerc Dijon (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital de la Timone CHU - APHM (TIMONE), Centre Référent des Troubles du Langage et des Apprentissages CHU Dijon (CRTLA ), Laboratoire de cytogénétique (CHU de Dijon), Regional council of Burgundy NIDCD/NIH |
| المصدر: | ISSN: 1018-4813. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2016 |
| المجموعة: | Université de Bourgogne (UB): HAL |
| مصطلحات موضوعية: | adhesion-like molecules, short-term, nmda receptor, down-syndrome, language, speech, expression, disorders, family, autism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience ; Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-01405814; https://u-bourgogne.hal.science/hal-01405814Test; PUBMEDCENTRAL: PMC4867460 |
| DOI: | 10.1038/ejhg.2015.221 |
| الإتاحة: | https://doi.org/10.1038/ejhg.2015.221Test https://u-bourgogne.hal.science/hal-01405814Test |
| رقم الانضمام: | edsbas.566A03BF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ejhg.2015.221 |
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