A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y.
Neuron
; 106(5): 759-768.e7, 2020 06 03.
Article
en En
| MEDLINE
| ID: mdl-32243781
ABSTRACT
Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing â¼97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Moléculas de Adhesión Celular Neuronal
/
Cromosomas Humanos X
/
Cromosomas Humanos Y
/
Neuronas
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos