Laumonnier F

References (3)

Title : Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment - Quartier_2019_Hum.Mutat_40_2021
Author(s) : Quartier A , Courraud J , Thi Ha T , McGillivray G , Isidor B , Rose K , Drouot N , Savidan MA , Feger C , Jagline H , Chelly J , Shaw M , Laumonnier F , Gecz J , Mandel JL , Piton A
Ref : Hum Mutat , 40 :2021 , 2019
Abstract : The X-linked NLGN3 gene, encoding a postsynaptic cell adhesion molecule, was involved in a nonsyndromic monogenic form of autism spectrum disorder (ASD) by the description of one unique missense variant, p.Arg451Cys (Jamain et al. 2003). We investigated here the pathogenicity of additional missense variants identified in two multiplex families with intellectual disability (ID) and ASD: c.1789C>T, p.Arg597Trp, previously reported by our group (Redin et al. 2014) and present in three affected cousins and c.1540C>T, p.Pro514Ser, identified in two affected brothers. Overexpression experiments in HEK293 and HeLa cell lines revealed that both variants affect the level of the mature NLGN3 protein, its localization at the plasma membrane and its presence as a cleaved form in the extracellular environment, even more drastically than what was reported for the initial p.Arg451Cys mutation. The variants also induced an unfolded protein response, probably due to the retention of immature NLGN3 proteins in the endoplasmic reticulum. In comparison, the c.1894A>G, p.Ala632Thr and c.1022T>C, p.Val341Ala variants, present in males from the general population, have no effect. Our report of two missense variants affecting the normal localization of NLGN3 in a total of five affected individuals reinforces the involvement of the NLGN3 gene in a neurodevelopmental disorder characterized by ID and ASD.
ESTHER : Quartier_2019_Hum.Mutat_40_2021
PubMedSearch : Quartier_2019_Hum.Mutat_40_2021
PubMedID: 31184401
Gene_locus related to this paper: human-NLGN3

Title : Autism and nonsyndromic mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level - Daoud_2009_Biol.Psychiatry_66_906
Author(s) : Daoud H , Bonnet-Brilhault F , Vedrine S , Demattei MV , Vourc'h P , Bayou N , Andres CR , Barthelemy C , Laumonnier F , Briault S
Ref : Biological Psychiatry , 66 :906 , 2009
Abstract : BACKGROUND: Pathogenic mutations in the X-linked Neuroligin 4 gene (NLGN4X) in autism spectrum disorders (ASDs) and/or mental retardation (MR) are rare. However, nothing is known regarding a possible altered expression level of NLGN4X that would be caused by mutations in regulatory sequences. We investigated this issue by analyzing these regions in patients with ASDs and no mutation in the NLGN4X coding sequence. METHODS: We studied 96 patients who met all DSM-IV criteria for autism. The entire coding sequence and the regulatory sequences of the NLGN4X gene were analyzed by polymerase chain reaction and direct sequencing. RESULTS: We identified a de novo 1 base pair (-335G>A) substitution located in the promoter region in a patient with autism and nonsyndromic profound MR. Interestingly, this variation is associated with an increased level of the NLGN4X transcript in the patient compared with male control subjects as well as his father. Further in vitro luciferase reporter and electrophoretic mobility shift assays confirmed, respectively, that this mutation increases gene expression and is probably caused by altered binding of transcription factors in the mutated promoter sequence. CONCLUSIONS: This result brings further insight about the phenotypic spectrum of NLGN4X mutations and suggests that the analysis of the expression level of NLGN4X might detect new cases.
ESTHER : Daoud_2009_Biol.Psychiatry_66_906
PubMedSearch : Daoud_2009_Biol.Psychiatry_66_906
PubMedID: 19545860

Title : X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family - Laumonnier_2004_Am.J.Hum.Genet_74_552
Author(s) : Laumonnier F , Bonnet-Brilhault F , Gomot M , Blanc R , David A , Moizard MP , Raynaud M , Ronce N , Lemonnier E , Calvas P , Laudier B , Chelly J , Fryns JP , Ropers HH , Hamel BC , Andres C , Barthelemy C , Moraine C , Briault S
Ref : American Journal of Human Genetics , 74 :552 , 2004
Abstract : A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.
ESTHER : Laumonnier_2004_Am.J.Hum.Genet_74_552
PubMedSearch : Laumonnier_2004_Am.J.Hum.Genet_74_552
PubMedID: 14963808
Gene_locus related to this paper: human-NLGN4X