Open AccessNot all neuroligin 3 and 4X missense variants lead to significant functional inactivation
Author(s) -
Xu Xiaojuan,
Hu Zhengmao,
Zhang Lusi,
Liu Hongfang,
Cheng Yuemei,
Xia Kun,
Zhang Xuehong
Publication year - 2017
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.793
Subject(s) - missense mutation , neuroligin , biology , lead (geology) , genetics , computational biology , mutation , gene , receptor , paleontology , excitatory postsynaptic potential
Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin ( NLGN ) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S ( NLGN 3), p.G84R ( NLGN 4X), p.Q162K ( NLGN 4X), and p.A283T ( NLGN 4X)] in four different unrelated patients have been identified by PCR and direct sequencing. Methods In this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK 293 cells expressing wild‐type and mutant neuroligin. Results We found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1–neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms. Conclusion Our data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.