Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases.
Cell Rep
; 38(11): 110517, 2022 03 15.
Article
em En
| MEDLINE
| ID: mdl-35294868
ABSTRACT
Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through "humanization" rescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.
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Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
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Receptores de Glicina
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Drosophila
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Transtornos do Neurodesenvolvimento
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Transtorno do Espectro Autista
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article