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Abstract：
Neuroligin 4 X-linked (NLGN4X) is an X-linked postsynaptic scaffolding protein, with functional role in excitatory synapsis development and maintenance, that has been associated with neuropsychiatric disorders such as intellectual disability, autism spectrum disorders (ASD), anxiety, attention deficit hyperactivity disorder (ADHD), and Tourette\'s syndrome. Chromosomal microarray analysis identified a paternally inherited, 445 Kb deletion on Xp22.3 that includes the entire NLGN4X in a 2.5 year old female (46,XX) with congenital hypotonia, strabismus, ASD, and increased aggressive behavioral issues. Her family history is significant for a mother with learning disabilities, a father with anxiety, major depressive disorder, and substance abuse, as well as two maternal half-brothers with developmental delays. X-inactivation studies in the proband\'s blood showed random X-inactivation despite the presence of an abnormal X chromosome. Furthermore, trio exome sequencing did not reveal any other deleterious variant that could explain her phenotype. Our report describes the first example of a paternally inherited NLGN4X microdeletion as the genetic etiology of ASD in a female proband, and the psychiatric phenotypes in the father. It also provides further evidence that NLGN4X is sensitive to dosage changes in females, and can contribute to a variety of psychiatric features within the same family.
摘要：
Neuroligin4X连锁（NLGN4X）是一种X连锁的突触后支架蛋白，在兴奋性突触发育和维持中具有功能作用，这与神经精神疾病如智力障碍有关，自闭症谱系障碍（ASD），焦虑,注意缺陷多动障碍（ADHD），和Tourette综合征.染色体微阵列分析确定了父系遗传，Xp22.3上的445Kb缺失，包括患有先天性肌张力减退的2.5岁女性（46，XX）中的整个NLGN4X，斜视,ASD,并增加了攻击性行为问题。她的家族史对于有学习障碍的母亲来说意义重大，一个焦虑的父亲，重度抑郁症,和药物滥用，以及两个有发育迟缓的母亲同父异母兄弟。先证者血液中的X失活研究显示，尽管存在异常的X染色体，但X失活是随机的。此外，三外显子组测序没有发现任何其他有害变异可以解释她的表型。我们的报告描述了父系遗传的NLGN4X微缺失作为女性先证者ASD的遗传病因的第一个例子，和父亲的精神病表型。它还提供了进一步的证据，表明NLGN4X对女性的剂量变化敏感，并且可以促进同一家庭中的各种精神病学特征。
