The Application of Clinical Genetics (Sep 2022)
Case Report of a Juvenile Patient with Autism Spectrum Disorder with a Novel Combination of Copy Number Variants in ADGRL3 (LPHN3) and Two Pseudogenes
Abstract
Martin H Maurer,1 Anja Kohler,1 Melanie Hudemann,1 Jerome Jüngling,2 Saskia Biskup,2,3 Martin Menzel1 1Mariaberg Hospital for Child and Adolescent Psychiatry, Gammertingen, Germany; 2Zentrum für Humangenetik, Tübingen, Germany; 3Center for Genomics and Transcriptomics, CeGaT GmbH, Tübingen, GermanyCorrespondence: Martin H Maurer, Mariaberg Hospital for Child and Adolescent Psychiatry, Burghaldenstraße 12, Gammertingen, 72501, Germany, Tel +49 7124 9237200, Fax +49 7124 923555, Email [email protected]: We report the finding of two copy number variants (CNVs) in a 12-year-old boy presenting both with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Clinical features included aggressive behavior, mood instability, suicidal statements, repetitive and restrictive behavior, sensitivity to noise, learning problems and dyslexia, though no intellectual disability was present. Using array-based comparative genomic hybridization (array-CGH), we identified two CNVs, both triplex duplications of 324 kb on 3p26.3, and 284 kb on 4q13.1, respectively. One of the CNVs is located on chromosome 4q13.1 in the region of the gene encoding for adhesion G protein-coupled receptor L3 (ADGRL3, former name: latrophilin-3, LPHN3), the other on chromosome 3p26.3 in the region of the two pseudogenes AC090043.1 and RPL23AP39. The patient described in the present study showed increased symptoms under methylphenidate treatment but responded positively to 3 mg per day of the atypical neuroleptic drug aripiprazole. To our knowledge, this is the first report of a CNV in the ADGRL3 gene and its first association with ASD in humans.Keywords: latrophilin-3, LPHN3, adhesion G protein-coupled receptor L3, ADGRL3, autism spectrum disorder, ASD
