BRIEF REPORTSAnalysis of the neuroligin 4Y gene in patients with autismYan, Jina; Feng, Jinonga; Schroer, Richardb; Li, Wenyana; Skinner, Cindyb; Schwartz, Charles E.b; Cook, Edwin H. Jrc; Sommer, Steve S.aAuthor Information aDepartment of Molecular Genetics, City of Hope National Medical Center, Duarte, California bGreenwood Genetic Center, Greenwood, South Carolina cInstitute for Juvenile Research, Department of Psychiatry, University of Illinois, Chicago, Illinois, USA Correspondence to Dr Steve S. Sommer, MD, PhD, Departments of Molecular Genetics and Molecular Diagnosis, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA Tel: +1 626 930 5497; fax: +1 626 301 8142; e-mail: [email protected] Received 9 August 2007 Accepted 14 January 2008 Psychiatric Genetics: August 2008 - Volume 18 - Issue 4 - p 204-207 doi: 10.1097/YPG.0b013e3282fb7fe6 Buy Metrics Abstract 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. © 2008 Lippincott Williams & Wilkins, Inc.