Abstract：
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.
摘要：
突触前膜中的神经素（NRXN）与称为神经素（NLGN）的突触后细胞粘附分子的相互作用对于这种突触功能至关重要。神经发育障碍强调突触功能受损以揭示病因。我们使用临床外显子组测序和染色体微阵列评估了NRXN和NLGN基因中编码直接位于神经精神疾病患者突触的分子的变体。我们提供了携带杂合NRXN1的病例的详细临床发现（c.190C>T，c.1679C>T和两个拷贝数变化[CNVs]），NRXN2(c.808dup，c.1901G>T)，NRXN3（c.3889C>T），和NLGN1(c.269>G，c.473T>A）基因变体。此外,在NRXN1中鉴定出三个新的变体(c.1679C>T)，NRXN3[c.3889C>T（p。Pro1297Ser)],和NLGN1[c.473T>A（p。Ile158Lys)]基因。在这项研究中，我们强调NRXN1基因的CNV的临床发现比NRXN1基因的单核苷酸变体引起更严重的临床表现。我们在两个具有相同诊断的无关病例中检测到具有低等位基因频率的NRXN2基因变体（c.808dup）。我们强调这种变体对未来研究的重要性。我们建议NRXN2，NRXN3和NLGN1基因，比NRXN1基因变异报道频率低，也可能与神经发育障碍有关。
