Rare heterozygous genetic variants of NRXN and NLGN gene families involved in synaptic function and their association with neurodevelopmental disorders.

Autor: Gerik-Celebi HB; Department of Medical Genetics, Balıkesir Ataturk City Hospital, Balıkesir, Turkey., Bolat H; Department of Medical Genetics, Balıkesir University Faculty of Medicine, Balıkesir, Turkey., Unsel-Bolat G; Department of Child and Adolescent Psychiatry, Balıkesir University Faculty of Medicine, Balıkesir, Turkey.
Jazyk: angličtina
Zdroj: Developmental neurobiology [Dev Neurobiol] 2024 Jul; Vol. 84 (3), pp. 158-168. Date of Electronic Publication: 2024 May 13.
DOI: 10.1002/dneu.22941
Abstrakt: The interaction of neurexins (NRXNs) in the presynaptic membrane with postsynaptic cell adhesion molecules called neuroligins (NLGNs) is critical for this synaptic function. Impaired synaptic functions are emphasized in neurodevelopmental disorders to uncover etiological factors. We evaluated variants in NRXN and NLGN genes encoding molecules located directly at the synapse in patients with neuropsychiatric disorders using clinical exome sequencing and chromosomal microarray. We presented detailed clinical findings of cases carrying heterozygous NRXN1 (c.190C > T, c.1679C > T and two copy number variations [CNVs]), NRXN2 (c.808dup, c.1901G > T), NRXN3 (c.3889C > T), and NLGN1 (c.269C > G, c.473T > A) gene variants. In addition, three novel variants were identified in the NRXN1 (c.1679C > T), NRXN3 [c.3889C > T (p.Pro1297Ser)], and NLGN1 [c.473T > A (p.Ile158Lys)] genes. We emphasize the clinical findings of CNVs of the NRXN1 gene causing a more severe clinical presentation than single nucleotide variants of the NRXN1 gene in this study. We detected an NRXN2 gene variant (c.808dup) with low allelic frequency in two unrelated cases with the same diagnosis. We emphasize the importance of this variant for future studies. We suggest that NRXN2, NRXN3, and NLGN1 genes, which are less frequently reported than NRXN1 gene variants, may also be associated with neurodevelopmental disorders.
(© 2024 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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