Dataset Information

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

ABSTRACT: 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.

SUBMITTER: Thevenon J

PROVIDER: S-EPMC4867460 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

Thevenon Julien J Souchay Céline C Seabold Gail K GK Dygai-Cochet Inna I Callier Patrick P Gay Sébastien S Corbin Lucie L Duplomb Laurence L Thauvin-Robinet Christel C Masurel-Paulet Alice A El Chehadeh Salima S Avila Magali M Minot Delphine D Guedj Eric E Chancenotte Sophie S Bonnet Marlène M Lehalle Daphne D Wang Ya-Xian YX Kuentz Paul P Huet Frédéric F Mosca-Boidron Anne-Laure AL Marle Nathalie N Petralia Ronald S RS Faivre Laurence L

European journal of human genetics : EJHG 20151021 6

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. ...[more]

PMID: 26486473

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Dataset Information

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

Publications

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits.

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