Yan Jin, Feng Jinong, Schroer Richard, Li Wenyan, Skinner Cindy, Schwartz Charles E, Cook Edwin H, Sommer Steve S
Department of Molecular Genetics, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
Psychiatr Genet. 2008 Aug;18(4):204-7. doi: 10.1097/YPG.0b013e3282fb7fe6.
Frameshift and missense mutations in the X-linked neuroligin 4 (NLGN4, MIM# 300427) and neuroligin 3 (NLGN3, MIM# 300336) genes have been identified in patients with autism, Asperger syndrome and mental retardation. We hypothesize that sequence variants in NLGN4Y are associated with autism or mental retardation. The coding sequences and splice junctions of the NLGN4Y gene were analyzed in 335 male samples (290 with autism and 45 with mental retardation). A total of 1.1 Mb of genomic DNA was sequenced. One missense variant, p.I679V, was identified in a patient with autism, as well as his father with learning disabilities. The I679 residue is highly conserved in three members of the neuroligin family. The absence of p.I679V in 2986 control Y chromosomes and the high similarity of NLGN4 and NLGN4Y are consistent with the hypothesis that p.I679V contributes to the etiology of autism. The presence of only one structural variant in our population of 335 males with autism/mental retardation, the unavailability of significant family cosegregation and an absence of functional assays are, however, important limitations of this study.
在患有自闭症、阿斯伯格综合征和智力迟钝的患者中，已发现X连锁神经连接蛋白4（NLGN4，MIM# 300427）和神经连接蛋白3（NLGN3，MIM# 300336）基因存在移码突变和错义突变。我们推测NLGN4Y基因中的序列变异与自闭症或智力迟钝有关。对335份男性样本（290例自闭症患者和45例智力迟钝患者）的NLGN4Y基因编码序列和剪接位点进行了分析。共对1.1 Mb的基因组DNA进行了测序。在一名自闭症患者及其患有学习障碍的父亲中，发现了一个错义变异p.I679V。I679残基在神经连接蛋白家族的三个成员中高度保守。在2986条对照Y染色体中未发现p.I679V，且NLGN4和NLGN4Y高度相似，这与p.I679V导致自闭症病因的假设一致。然而，在我们这335名患有自闭症/智力迟钝的男性群体中仅发现一种结构变异、缺乏显著的家族共分离情况以及未进行功能测定，是本研究的重要局限性。
