Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization.
Am J Med Genet A
; 185(3): 894-900, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33369065
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Tourette
/
Moléculas de Adhesión Celular Neuronal
/
Discapacidades del Desarrollo
/
Eliminación de Gen
/
Cromosomas Humanos X
/
Enfermedades Genéticas Ligadas al Cromosoma X
/
Genes Ligados a X
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article