Gerik-Celebi_2024_Dev.Neurobiol__

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.