Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization. Am J Med Genet A 2021 Mar;185(3):894-900
Date
12/29/2020Pubmed ID
33369065DOI
10.1002/ajmg.a.62025Scopus ID
2-s2.0-85099517534 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Kopp N, Amarillo I, Martinez-Agosto J, Quintero-Rivera FAuthor
Nathan Kopp PhD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAggression
Anxiety
Autism Spectrum Disorder
Cell Adhesion Molecules, Neuronal
Child Behavior Disorders
Child, Preschool
Chromosomes, Human, X
Developmental Disabilities
Female
Gene Deletion
Genes, X-Linked
Genetic Diseases, X-Linked
Humans
In Situ Hybridization, Fluorescence
Male
Medical History Taking
Microarray Analysis
Paternal Inheritance
Seizures
Strabismus
Substance-Related Disorders
Tourette Syndrome
X Chromosome Inactivation
