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Chromosomal microarray analysis identified a paternally inherited, 445 Kb deletion on Xp22.3 that includes the entire <jats:italic>NLGN4X<\/jats:italic> 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\u2010brothers with developmental delays. X\u2010inactivation studies in the proband's blood showed random X\u2010inactivation 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 <jats:italic>NLGN4X<\/jats:italic> microdeletion as the genetic etiology of ASD in a female proband, and the psychiatric phenotypes in the father. It also provides further evidence that <jats:italic>NLGN4X<\/jats:italic> is sensitive to dosage changes in females, and can contribute to a variety of psychiatric features within the same family.<\/jats:p>","DOI":"10.1002\/ajmg.a.62025","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T08:14:43Z","timestamp":1608884083000},"page":"894-900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pathogenic paternally inherited <scp><i>NLGN4X<\/i><\/scp> deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0858-3242","authenticated-orcid":false,"given":"Nathan","family":"Kopp","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center University of California, Los Angeles, David Geffen School of Medicine  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Amarillo","sequence":"additional","affiliation":[{"name":"Department of Pathology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-6949","authenticated-orcid":false,"given":"Julian","family":"Martinez\u2010Agosto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Genetics, UCLA Clinical Genomics Center University of California, Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-6209","authenticated-orcid":false,"given":"Fabiola","family":"Quintero\u2010Rivera","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, UCLA Clinical Genomics Center University of California, Los Angeles, David Geffen School of Medicine  Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine University of California, Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/nrg3940","article-title":"ACMG guides on the interpretation of sequence variants","volume":"16","author":"Bahcall O. 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